PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 30993382-10 2019 Western blot analyses showed that p-Akt played a key role in determining the sensitivities of A549, A549GR, H1650, and H1650GR to gefitinib or AZD9291. Gefitinib 130-139 AKT serine/threonine kinase 1 Homo sapiens 36-39 31196210-8 2019 Combination treatment with curcumin and gefitinib markedly downregulated EGFR activity through suppressing Sp1 and blocking interaction of Sp1 and HADC1, and markedly suppressed receptor tyrosine kinases as well as ERK/MEK and AKT/S6K pathways in the resistant NSCLC cells. Gefitinib 40-49 AKT serine/threonine kinase 1 Homo sapiens 227-230 30701693-10 2019 The combination of TMS and gefitinib promoted apoptosis also by miR-345 and miR-498 targeting the MAPK/c-Fos and AKT/Bcl-2 signalling pathways. Gefitinib 27-36 AKT serine/threonine kinase 1 Homo sapiens 113-116 29637613-8 2018 Moreover, gefitinib dramatically reduced p-EGFR and p-HER2 levels in the cell lines tested, and sensitivity to gefitinib was enhanced through dual silencing of EGFR and HER2 via suppression of AKT and ERK activation. Gefitinib 10-19 AKT serine/threonine kinase 1 Homo sapiens 193-196 30701693-0 2019 Trans-3,5,4 -trimethoxystilbene reduced gefitinib resistance in NSCLCs via suppressing MAPK/Akt/Bcl-2 pathway by upregulation of miR-345 and miR-498. Gefitinib 40-49 AKT serine/threonine kinase 1 Homo sapiens 92-95 30106149-3 2018 A combination of gefitinib and GGTI-298 amplified the inhibition of the EGFR-AKT signaling pathway. Gefitinib 17-26 AKT serine/threonine kinase 1 Homo sapiens 77-80 29215723-3 2018 Furthermore, cholesterol-depleted enhanced gefitinib inhibit phosphorylation of EGFR, Akt-1, MEK1/2, and ERK1/2 and these were reversed in cholesterol add-back experiments. Gefitinib 43-52 AKT serine/threonine kinase 1 Homo sapiens 86-91 30660770-8 2019 In addition, eEF1A2 and STAT1 siRNA transfections suggested that both STAT1 and eEF1A2 prevent AKT phosphorylation known for enhancing gefitinib resistance in NSCLC. Gefitinib 135-144 AKT serine/threonine kinase 1 Homo sapiens 95-98 29637613-8 2018 Moreover, gefitinib dramatically reduced p-EGFR and p-HER2 levels in the cell lines tested, and sensitivity to gefitinib was enhanced through dual silencing of EGFR and HER2 via suppression of AKT and ERK activation. Gefitinib 111-120 AKT serine/threonine kinase 1 Homo sapiens 193-196 29344641-5 2018 Gefitinib/MK-2206 treatment synergistically decreased the mTOR signaling target substrates along with the downregulation of ribosomal protein S6 (RPS6), a marker of cell proliferation and target substrate of the AKT-mTOR signaling pathway. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 212-215 29568946-0 2018 Gefitinib inhibits malignant melanoma cells through the VEGF/AKT signaling pathway. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 61-64 29568946-13 2018 In addition, gefitinib significantly downregulated the mRNA and protein expression levels of VEGF and AKT, and these changes were dose-dependent (P<0.05). Gefitinib 13-22 AKT serine/threonine kinase 1 Homo sapiens 102-105 29568946-14 2018 Taken together, gefitinib suppressed MM cell proliferation and invasion in vitro by regulating the VEGF/AKT signaling pathway. Gefitinib 16-25 AKT serine/threonine kinase 1 Homo sapiens 104-107 29480364-4 2018 The effect of radiation, 5-fluorouracil (5-Fu), and gefitinib on the EGFR, AKT, and ERK1/2 activation in H1975 cells was determined by Western blot. Gefitinib 52-61 AKT serine/threonine kinase 1 Homo sapiens 75-78 29928355-9 2018 Phosphorylated-protein kinase B (p-Akt), which is downstream of miR-21, was downregulated following gefitinib treatment; however, R/exo pretreatment elevated p-Akt levels and promoted the activation of Akt. Gefitinib 100-109 AKT serine/threonine kinase 1 Homo sapiens 35-38 29269300-9 2018 Downregulation of GAS7 expression could antagonize gefitinib re-sensitivity in PC9GR mediated by knockdown of miR-181a via AKT/ERK pathways and epithelial-to-mesenchymal transition markers. Gefitinib 51-60 AKT serine/threonine kinase 1 Homo sapiens 123-126 29487526-7 2018 Moreover, the knockdown of MIAT significantly sensitized PC9 and gefitinib-resistant PC9 cells to gefitinib in vitro and in vivo, and increased the expression of miR-34a and inactivated PI3K/Akt signaling. Gefitinib 65-74 AKT serine/threonine kinase 1 Homo sapiens 191-194 29487526-9 2018 Taken together, our findings demonstrated that knockdown of MIAT by siRNA enhances lung cancer cells to gefitinib through the PI3K/Akt signaling pathway by epigenetically regulating miR-34a. Gefitinib 104-113 AKT serine/threonine kinase 1 Homo sapiens 131-134 28577939-4 2017 RESULTS: MTT assays presented that CSE claimed antagonistic effect on gefitinib sensitivity via the up-regulated half maximal inhibitory concentration (IC50) values, western blot showed that CSE instigated EGFR, AKT phosphorylation, while N-Acetyl-l-Cysteine (NAC) could alleviate gefitinib resistance and abort the aberrant phosphorylation in both PC-9 and A549 cells. Gefitinib 70-79 AKT serine/threonine kinase 1 Homo sapiens 212-215 29080795-0 2017 PPARgamma agonist efatutazone and gefitinib synergistically inhibit the proliferation of EGFR-TKI-resistant lung adenocarcinoma cells via the PPARgamma/PTEN/Akt pathway. Gefitinib 34-43 AKT serine/threonine kinase 1 Homo sapiens 157-160 28828595-6 2017 RESULTS: Cal27, OSC19, and SCC25 cells treated with gefitinib 1 muM demonstrated reduced phosphorylation of EGFR, AKT, and ERK proteins with very limited inhibition of proliferation. Gefitinib 52-61 AKT serine/threonine kinase 1 Homo sapiens 114-117 29033690-7 2017 Consistently, the dual inhibition of EGFR and BRAF, through combination therapy with PLX4032 and gefitinib, resulted in prevention of EGFR phosphorylation and sustained inhibition of ERK and AKT signaling and cell proliferation. Gefitinib 97-106 AKT serine/threonine kinase 1 Homo sapiens 191-194 28713965-0 2017 Dihydroartemisinin and gefitinib synergistically inhibit NSCLC cell growth and promote apoptosis via the Akt/mTOR/STAT3 pathway. Gefitinib 23-32 AKT serine/threonine kinase 1 Homo sapiens 105-108 28713965-10 2017 DHA and gefitinib co-administration also downregulated the expression levels of phosphorylated (p)-Akt, p-mechanistic target of rapamycin, p-signal transducer and activator of transcription 3 and B-cell lymphoma 2 (Bcl-2), and upregulated the expression of Bcl-2-associated X protein. Gefitinib 8-17 AKT serine/threonine kinase 1 Homo sapiens 99-102 28101246-15 2016 Upregulation of microRNA-200b led to the elevated sensitivity of glioma cells to gefitinib, and this effect may be explained as microRNA-200b being able to inhibit the expression of IGF-1R, thereby reducing the activation of downstream phosphoinositide 3-kinase/AKT and mitogen-activated protein kinase signaling pathways. Gefitinib 81-90 AKT serine/threonine kinase 1 Homo sapiens 262-265 28529576-0 2017 Increased MIR31HG lncRNA expression increases gefitinib resistance in non-small cell lung cancer cell lines through the EGFR/PI3K/AKT signaling pathway. Gefitinib 46-55 AKT serine/threonine kinase 1 Homo sapiens 130-133 28529576-7 2017 As expected, MIR31HG lncRNA knockdown sensitized PC9-R cells to gefitinib, and further experiments revealed that turning off the EGFR/PI3K/AKT signaling pathway activated expression of p53 in PC9-R cells transfected with si-MIR31HG. Gefitinib 64-73 AKT serine/threonine kinase 1 Homo sapiens 139-142 28529576-10 2017 Furthermore, overexpression of MIR31HG lncRNAs may contribute to gefitinib resistance in PC9-R cells through the EGFR/PI3K/AKT pathway, which impacts on cell proliferation, apoptosis and the cell cycle. Gefitinib 65-74 AKT serine/threonine kinase 1 Homo sapiens 123-126 27930974-14 2017 Further in gefitinib resistant xenograft model, miR-200c enhanced sensitivity of gefitinib and induced apoptosis significantly through PI3K/Akt signaling pathway and targeting ZEB1. Gefitinib 11-20 AKT serine/threonine kinase 1 Homo sapiens 140-143 27930974-14 2017 Further in gefitinib resistant xenograft model, miR-200c enhanced sensitivity of gefitinib and induced apoptosis significantly through PI3K/Akt signaling pathway and targeting ZEB1. Gefitinib 81-90 AKT serine/threonine kinase 1 Homo sapiens 140-143 27989877-0 2016 Chinese herbal medicine Fuzheng Kang-Ai decoction sensitized the effect of gefitinib on inhibition of human lung cancer cells through inactivating PI3-K/Akt -mediated suppressing MUC1 expression. Gefitinib 75-84 AKT serine/threonine kinase 1 Homo sapiens 153-156 28881753-7 2017 The administration of various concentrations of gefitinib to HER3-knockdown cells enhanced antitumour activity and sensitivity due to the downregulation of protein phosphorylation via PI3K/AKT and ERK signalling. Gefitinib 48-57 AKT serine/threonine kinase 1 Homo sapiens 189-192 27930974-0 2017 miR-200c enhances sensitivity of drug-resistant non-small cell lung cancer to gefitinib by suppression of PI3K/Akt signaling pathway and inhibites cell migration via targeting ZEB1. Gefitinib 78-87 AKT serine/threonine kinase 1 Homo sapiens 111-114 28093061-0 2017 Polyphyllin II Restores Sensitization of the Resistance of PC-9/ZD Cells to Gefitinib by a Negative Regulation of the PI3K/Akt/mTOR Signaling Pathway. Gefitinib 76-85 AKT serine/threonine kinase 1 Homo sapiens 123-126 28093061-9 2017 PP II elevated sensitization of gefitinib through targeting the PI3K/Akt/mTOR. Gefitinib 32-41 AKT serine/threonine kinase 1 Homo sapiens 69-72 27716616-3 2016 In a cell line model where Met amplification has previously been shown to contribute to gefitinib resistance, Ran knockdown sensitized cells to gefitinib-mediated inhibition of Akt and ERK1/2 phosphorylation and consequently reduced cell proliferation. Gefitinib 144-153 AKT serine/threonine kinase 1 Homo sapiens 177-180 27877053-5 2016 The combination of gefitinib and vorinostat synergistically reduced cell growth and strongly induced apoptosis through inhibition of the insulin-like growth factor-1 receptor/protein kinase B (IGF-1R/AKT)-dependent signaling pathway. Gefitinib 19-28 AKT serine/threonine kinase 1 Homo sapiens 200-203 27989877-11 2016 Mechanistically, we showed that the phosphorylation of Akt, protein expressions of p65 and MUC1 were suppressed by FZKA and even more responses were observed in the FZKA and gefitinib combining. Gefitinib 174-183 AKT serine/threonine kinase 1 Homo sapiens 55-58 27989877-14 2016 In line with the above, our results confirmed the synergistic effects of FZKA and gefitinib combination on tumor growth, the phosphorylation of Akt, and protein expression of p65 and MUC1 in vivo. Gefitinib 82-91 AKT serine/threonine kinase 1 Homo sapiens 144-147 27494877-0 2016 FOXM1 confers resistance to gefitinib in lung adenocarcinoma via a MET/AKT-dependent positive feedback loop. Gefitinib 28-37 AKT serine/threonine kinase 1 Homo sapiens 71-74 27690301-9 2016 Thus, these results indicate that the miR-128/c-met pathway enhances the gefitinib sensitivity of the lung cancer stem cells by suppressing the PI3K/AKT pathway. Gefitinib 73-82 AKT serine/threonine kinase 1 Homo sapiens 149-152 27690301-0 2016 MiR-128 reverses the gefitinib resistance of the lung cancer stem cells by inhibiting the c-met/PI3K/AKT pathway. Gefitinib 21-30 AKT serine/threonine kinase 1 Homo sapiens 101-104 27629794-9 2016 In summary, our results indicate that gefitinib effectively enhances TRAIL-induced apoptosis, likely via autophagy and JNK- mediated death receptor expression and phosphorylation of Akt and ERK. Gefitinib 38-47 AKT serine/threonine kinase 1 Homo sapiens 182-185 27283902-9 2016 Furthermore, the combination of PA-MSHA plus Gefitinib resulted in caspase-3/caspase-9 cleavage and increased inhibition of EGFR-dependent activation of AKT and ERK phosphorylation. Gefitinib 45-54 AKT serine/threonine kinase 1 Homo sapiens 153-156 27346398-11 2016 Western blot data showed that the expression levels of LC3 and p-Akt were decreased in the combined groups than that of the gefitinib alone group, while the p-PTEN, caspase-3 and caspase-9 were increased. Gefitinib 124-133 AKT serine/threonine kinase 1 Homo sapiens 65-68 27698894-5 2016 In this study, we demonstrated that AKT-STAT3 pathway could be a potential target for regulating the surface expression of PD-L1 on NSCLCs with aberrant EGFR activity and, further, the inhibition of AKT or STAT3 activity could down-regulate the expression of PD-L1 even in gefitinib-resistant NSCLCs. Gefitinib 273-282 AKT serine/threonine kinase 1 Homo sapiens 36-39 27698894-5 2016 In this study, we demonstrated that AKT-STAT3 pathway could be a potential target for regulating the surface expression of PD-L1 on NSCLCs with aberrant EGFR activity and, further, the inhibition of AKT or STAT3 activity could down-regulate the expression of PD-L1 even in gefitinib-resistant NSCLCs. Gefitinib 273-282 AKT serine/threonine kinase 1 Homo sapiens 199-202 27347100-0 2016 Gefitinib induces lung cancer cell autophagy and apoptosis via blockade of the PI3K/AKT/mTOR pathway. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 84-87 27347100-8 2016 Furthermore, western blot analysis demonstrated that gefitinib treatment led to the downregulation of PI3K, AKT, pAKT, mTOR and phosphorylated-mTOR protein expression in A549 cells but not A549-GR cells. Gefitinib 53-62 AKT serine/threonine kinase 1 Homo sapiens 108-111 27347100-10 2016 In conclusion, the results of the present study indicate that gefitinib promotes autophagy and apoptosis of lung cancer cells via blockade of the PI3K/AKT/mTOR pathway, which leads to lung cancer cell death. Gefitinib 62-71 AKT serine/threonine kinase 1 Homo sapiens 151-154 27346398-12 2016 CONCLUSIONS: Autophagy inhibitor may enhance the sensitivity to gefitinib in MDA-MB-468 and MDA-MB-231 cells by activation of the PTEN/P13K/Akt pathway. Gefitinib 64-73 AKT serine/threonine kinase 1 Homo sapiens 140-143 26203858-0 2015 Reciprocal positive regulation between Cx26 and PI3K/Akt pathway confers acquired gefitinib resistance in NSCLC cells via GJIC-independent induction of EMT. Gefitinib 82-91 AKT serine/threonine kinase 1 Homo sapiens 53-56 27125283-0 2016 Anticancer Effects of Paris Saponins by Apoptosis and PI3K/AKT Pathway in Gefitinib-Resistant Non-Small Cell Lung Cancer. Gefitinib 74-83 AKT serine/threonine kinase 1 Homo sapiens 59-62 26870244-11 2016 Phosphoinositide 3-kinase (PI3K)/Akt activation was observed in PC9/G cells in the presence of gefitinib and the sensitivity of PC9/G cells to gefitinib was also able to be restored by PI3K/Akt pathway inhibitor LY294002. Gefitinib 143-152 AKT serine/threonine kinase 1 Homo sapiens 190-193 26870244-13 2016 These findings suggest that integrin beta1 signaling via the PI3K/Akt pathway may be a significant mechanism underlying gefitinib resistance, and may potentially present an alternative therapeutic target for the treatment of NSCLC unresponsive to EGFR inhibitors. Gefitinib 120-129 AKT serine/threonine kinase 1 Homo sapiens 66-69 26517520-7 2015 Treatment with 244-MPT could substantially reduce the phosphorylation of EGFR and its downstream signaling pathways, including Akt and ERK1/2 in gefitinib-sensitive and -resistant cell lines. Gefitinib 145-154 AKT serine/threonine kinase 1 Homo sapiens 127-130 26063323-11 2015 In the in vivo model, NCTD plus gefitinib resulted in marked regression of tumor growth associated with inhibition of Akt phosphorylation in cancer cells. Gefitinib 32-41 AKT serine/threonine kinase 1 Homo sapiens 118-121 26870244-11 2016 Phosphoinositide 3-kinase (PI3K)/Akt activation was observed in PC9/G cells in the presence of gefitinib and the sensitivity of PC9/G cells to gefitinib was also able to be restored by PI3K/Akt pathway inhibitor LY294002. Gefitinib 95-104 AKT serine/threonine kinase 1 Homo sapiens 33-36 26870244-11 2016 Phosphoinositide 3-kinase (PI3K)/Akt activation was observed in PC9/G cells in the presence of gefitinib and the sensitivity of PC9/G cells to gefitinib was also able to be restored by PI3K/Akt pathway inhibitor LY294002. Gefitinib 143-152 AKT serine/threonine kinase 1 Homo sapiens 33-36 26622906-6 2015 Treatment of A549 cells with gefitinib alone reduced the expression level of the activated form of Akt, and the combination of the two drugs showed stronger inhibition of phosphorylated-Akt and phosphorylated-extracellular signal-regulated kinases. Gefitinib 29-38 AKT serine/threonine kinase 1 Homo sapiens 99-102 26622906-6 2015 Treatment of A549 cells with gefitinib alone reduced the expression level of the activated form of Akt, and the combination of the two drugs showed stronger inhibition of phosphorylated-Akt and phosphorylated-extracellular signal-regulated kinases. Gefitinib 29-38 AKT serine/threonine kinase 1 Homo sapiens 186-189 26203858-9 2015 Cx26-mediated EMT and gefitinib resistance were significantly blocked by inhibition of PI3K/Akt pathway. Gefitinib 22-31 AKT serine/threonine kinase 1 Homo sapiens 92-95 26203858-11 2015 In conclusion, the reciprocal positive regulation between Cx26 and PI3K/Akt signaling contributes to acquired gefitinib resistance in NSCLC cells by promoting EMT via a GJIC-independent manner. Gefitinib 110-119 AKT serine/threonine kinase 1 Homo sapiens 72-75 25653196-0 2015 EGF-stimulated AKT activation is mediated by EGFR recycling via an early endocytic pathway in a gefitinib-resistant human lung cancer cell line. Gefitinib 96-105 AKT serine/threonine kinase 1 Homo sapiens 15-18 25588160-0 2015 Combination of SF1126 and gefitinib induces apoptosis of triple-negative breast cancer cells through the PI3K/AKT-mTOR pathway. Gefitinib 26-35 AKT serine/threonine kinase 1 Homo sapiens 110-113 25588160-7 2015 Moreover, phosphorylated AKT (p-AKT) and 70 kDa ribosomal protein S6-kinase (p-p70S6K) were also inhibited by the gefitinib and SF1126 combination, which may be responsible for the apoptosis. Gefitinib 114-123 AKT serine/threonine kinase 1 Homo sapiens 25-28 25588160-7 2015 Moreover, phosphorylated AKT (p-AKT) and 70 kDa ribosomal protein S6-kinase (p-p70S6K) were also inhibited by the gefitinib and SF1126 combination, which may be responsible for the apoptosis. Gefitinib 114-123 AKT serine/threonine kinase 1 Homo sapiens 32-35 25588160-8 2015 Gefitinib combined with SF1126 could induce cell apoptosis in TNBC cells and this effect was mediated through the EGFR-PI3K-AKT-mTOR-p70S6K pathway. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 124-127 25662161-0 2015 Down-regulation of ERK1/2 and AKT-mediated X-ray repair cross-complement group 1 protein (XRCC1) expression by Hsp90 inhibition enhances the gefitinib-induced cytotoxicity in human lung cancer cells. Gefitinib 141-150 AKT serine/threonine kinase 1 Homo sapiens 30-33 25662161-1 2015 Gefitinib (Iressa(R), ZD1839) is a selective epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that blocks growth factor-mediated cell proliferation and extracellular signal-regulated kinases 1/2 (ERK1/2) and AKT signaling activation. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 229-232 25662161-1 2015 Gefitinib (Iressa(R), ZD1839) is a selective epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that blocks growth factor-mediated cell proliferation and extracellular signal-regulated kinases 1/2 (ERK1/2) and AKT signaling activation. Gefitinib 22-28 AKT serine/threonine kinase 1 Homo sapiens 229-232 25662161-4 2015 However, the role of ERK1/2 and AKT-mediated XRCC1 expression in gefitinib alone or combination with an Hsp90 inhibitor-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Gefitinib 65-74 AKT serine/threonine kinase 1 Homo sapiens 32-35 25662161-5 2015 In this study, gefitinib treatment decreased XRCC1 mRNA and protein expression through ERK1/2 and AKT inactivation in two NSCLC cells, A549 and H1975. Gefitinib 15-24 AKT serine/threonine kinase 1 Homo sapiens 98-101 25662161-9 2015 Furthermore, transfection with constitutive active MKK1 or AKT vectors rescued the XRCC1 protein level as well as the cell survival suppressed by an Hsp90 inhibitor and gefitinib. Gefitinib 169-178 AKT serine/threonine kinase 1 Homo sapiens 59-62 25674002-12 2015 CONCLUSION: Taken together, we suggest that NVP-BEZ235 inhibits gefitinib-resistant tumor growth by downregulating PI3K/AKT/mTOR phosphorylation. Gefitinib 64-73 AKT serine/threonine kinase 1 Homo sapiens 120-123 25454348-5 2015 In addition, AKT is constitutively phosphorylated in these cells and is resistant to gefitinib. Gefitinib 85-94 AKT serine/threonine kinase 1 Homo sapiens 13-16 26176330-6 2015 This may be explained by the observation that the depletion of ARF1 suppressed gefitinib-mediated activation of key mediators of survival such as ERK1/2, AKT and Src, while enhancing cascades leading to apoptosis such as the p38MAPK and JNK pathways, modifying the Bax/Bcl2 ratio and cytochrome c release. Gefitinib 79-88 AKT serine/threonine kinase 1 Homo sapiens 154-157 25623760-12 2014 The combination of Ad-p53 and gefitinib significantly down-regulated p-Akt (S473)(P < 0.01) and up-regulated caspase-9 and cleaved caspase-3 (P < 0.01 for both). Gefitinib 30-39 AKT serine/threonine kinase 1 Homo sapiens 71-74 25674002-0 2015 NVP-BEZ235 overcomes gefitinib-acquired resistance by down-regulating PI3K/AKT/mTOR phosphorylation. Gefitinib 21-30 AKT serine/threonine kinase 1 Homo sapiens 75-78 25488183-0 2015 Enoxaparin sensitizes human non-small-cell lung carcinomas to gefitinib by inhibiting DOCK1 expression, vimentin phosphorylation, and Akt activation. Gefitinib 62-71 AKT serine/threonine kinase 1 Homo sapiens 134-137 25623760-16 2014 CONCLUSIONS: Wild-type p53 may reverse the sensitivity of MDA-MB-468 cells to gefitinib through down-regulation of the PI3K/Akt pathway. Gefitinib 78-87 AKT serine/threonine kinase 1 Homo sapiens 124-127 25275600-8 2014 Western blot analysis shows gefitinib reduces both basal and B-cell receptor (BCR)-stimulated phosphorylation of Syk/ZAP-70, ERK, and Akt in ZAP-70+ CLL cells. Gefitinib 28-37 AKT serine/threonine kinase 1 Homo sapiens 134-137 24957682-0 2014 AKT inhibition synergistically enhances growth-inhibitory effects of gefitinib and increases apoptosis in non-small cell lung cancer cell lines. Gefitinib 69-78 AKT serine/threonine kinase 1 Homo sapiens 0-3 24374738-0 2014 The PI3K/AKT pathway promotes gefitinib resistance in mutant KRAS lung adenocarcinoma by a deacetylase-dependent mechanism. Gefitinib 30-39 AKT serine/threonine kinase 1 Homo sapiens 9-12 25058005-7 2014 Moreover, over-expression of miR-21 significantly decreased gefitinib sensitivity by down-regulating Pten expression and activating Akt and ERK pathways in pc-9 cells, while miR-21 knockdown dramatically restored gefitinib sensitivity of pc-9/GR cells by up-regulation of Pten expression and inactivation of AKT and ERK pathways, in vivo and in vitro. Gefitinib 60-69 AKT serine/threonine kinase 1 Homo sapiens 132-135 25058005-7 2014 Moreover, over-expression of miR-21 significantly decreased gefitinib sensitivity by down-regulating Pten expression and activating Akt and ERK pathways in pc-9 cells, while miR-21 knockdown dramatically restored gefitinib sensitivity of pc-9/GR cells by up-regulation of Pten expression and inactivation of AKT and ERK pathways, in vivo and in vitro. Gefitinib 60-69 AKT serine/threonine kinase 1 Homo sapiens 308-311 24840891-9 2014 In addition, the combination of pemetrexed and gefitinib decreased the levels of phosphorylated AKT, phosphorylated extracellular-signal-regulated kinase and B-cell lymphoma 2 as compared with those in the control. Gefitinib 47-56 AKT serine/threonine kinase 1 Homo sapiens 96-99 24374738-6 2014 The activation of AKT was associated with disease progression in tumors with wild-type EGFR from patients treated with gefitinib (phase II clinical trial IFCT0401). Gefitinib 119-128 AKT serine/threonine kinase 1 Homo sapiens 18-21 24374738-10 2014 The PI3K/AKT pathway is thus a major pathway contributing to gefitinib resistance in lung tumors with KRAS mutation, through the regulation of the BAX/Ku70 interaction. Gefitinib 61-70 AKT serine/threonine kinase 1 Homo sapiens 9-12 24884778-13 2014 The Western blotting results showed that MTE MTE+gefitinib treatment further enhanced the suppression of gefitinib on cell growth and apoptosis pathway such as ERK1/2 and PI3K/Akt/mTOR. Gefitinib 49-58 AKT serine/threonine kinase 1 Homo sapiens 176-179 24268810-6 2014 Our data revealed that let-7c increases gefitinib sensitivity by repressing RAS and inactivating the phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathways. Gefitinib 40-49 AKT serine/threonine kinase 1 Homo sapiens 134-137 24884778-13 2014 The Western blotting results showed that MTE MTE+gefitinib treatment further enhanced the suppression of gefitinib on cell growth and apoptosis pathway such as ERK1/2 and PI3K/Akt/mTOR. Gefitinib 105-114 AKT serine/threonine kinase 1 Homo sapiens 176-179 24486412-6 2014 Blocking the TGF-alpha/EGFR pathway by gefitinib, a specific EGFR inhibitor, reduced the activation of STAT (signal transducer and activator of transcription) 3, AKT and ERK (extracellular signal-regulated kinase), and synergized with sorafenib to inhibit proliferation and induce apoptosis of hypoxic HCC cells. Gefitinib 39-48 AKT serine/threonine kinase 1 Homo sapiens 162-165 24631288-6 2014 Both insulin treatment and AKT overexpression markedly increased p-beta-catenin and survivin levels, even in the presence of gefitinib and simvastatin. Gefitinib 125-134 AKT serine/threonine kinase 1 Homo sapiens 27-30 24146879-3 2013 Our data show that elevation of autophagy in gefitinib-treated breast cancer cells correlated with downregulation of AKT and ERK1/2 signaling early in the course of treatment. Gefitinib 45-54 AKT serine/threonine kinase 1 Homo sapiens 117-120 24341609-9 2013 In human MPNST cell lines ST88-14 and STS26T, inhibition of EGFR by siRNA or Gefitinib led to decreased cell proliferation, migration, and invasion accompanied by attenuation of PI3K/AKT and MAPK pathways. Gefitinib 77-86 AKT serine/threonine kinase 1 Homo sapiens 183-186 23962905-5 2013 Compared with the monotherapy, the combined treatment of crizotinib and gefitinib induced apoptosis and significantly inhibited the growth of cells in the presence of HGF by blocking the MET/PI3K/Akt pathway. Gefitinib 72-81 AKT serine/threonine kinase 1 Homo sapiens 196-199 24337846-9 2013 It was also found that the mRNA expression levels of these genes were down-regulated by NVP-BKM120 (1 mumol/L), and NVP-BKM120 (1 mumol/L) or NVP-BKM120 (1 mumol/L) plus gefitinib (1 mumol/L) obviously inhibited the activation of Akt, S6 and 4E-BP1 as compared with control group, but single use of gefitinib (1 mumol/L) exerted no significant effect. Gefitinib 170-179 AKT serine/threonine kinase 1 Homo sapiens 230-233 24337846-9 2013 It was also found that the mRNA expression levels of these genes were down-regulated by NVP-BKM120 (1 mumol/L), and NVP-BKM120 (1 mumol/L) or NVP-BKM120 (1 mumol/L) plus gefitinib (1 mumol/L) obviously inhibited the activation of Akt, S6 and 4E-BP1 as compared with control group, but single use of gefitinib (1 mumol/L) exerted no significant effect. Gefitinib 299-308 AKT serine/threonine kinase 1 Homo sapiens 230-233 24337846-11 2013 It was also concluded that NVP-BKM120 could overcome the acquired resistance to gefitinib by down-regulating the phosphorylated protein in PI3K/AKT signal pathways in H1975 cells, but it could not enhance the sensitivity of H1975 cells to gefitinib. Gefitinib 80-89 AKT serine/threonine kinase 1 Homo sapiens 144-147 24280348-0 2013 Gefitinib resistance resulted from STAT3-mediated Akt activation in lung cancer cells. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 50-53 24280348-3 2013 In this study, we have discovered a STAT3-dependent Akt activation that impairs the efficacy of gefitinib. Gefitinib 96-105 AKT serine/threonine kinase 1 Homo sapiens 52-55 23959460-12 2013 Pemetrexed induced an EGFR-mediated activation of the phosphatidylinositol 3-kinase/AKT and ERK pathway, which was inhibited by gefitinib. Gefitinib 128-137 AKT serine/threonine kinase 1 Homo sapiens 84-87 23849826-12 2013 Gefitinib inhibits EGFR and AKT phosphorylation and Cetuximab induces EGFR phosphorylation but inhibits signalling to AKT induced with EGF. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 28-31 24071646-5 2013 Atorvastatin (1 muM) plus gefitinib treatment inhibited proliferation, promoted cell apoptosis, and reduced the AKT activity in KRAS mutant NSCLC cells compared with gefitinib alone. Gefitinib 26-35 AKT serine/threonine kinase 1 Homo sapiens 112-115 24071646-6 2013 Atorvastatin (5 muM) further enhanced the gefitinib cytotoxicity through concomitant inhibition of AKT and ERK activity. Gefitinib 42-51 AKT serine/threonine kinase 1 Homo sapiens 99-102 24325059-8 2013 Results of Western blot showed the protein expressions of p-EGFR, p-Met, p-Akt, and p-mTOR in H1975 cells could be markedly down-regulated by bufalin plus gefitinib. Gefitinib 155-164 AKT serine/threonine kinase 1 Homo sapiens 75-78 23111983-0 2013 Apoptosis induced by benzyl isothiocyanate in gefitinib-resistant lung cancer cells is associated with Akt/MAPK pathways and generation of reactive oxygen species. Gefitinib 46-55 AKT serine/threonine kinase 1 Homo sapiens 103-106 23525575-11 2013 Exposure to the combination of RAD001 and gefitinib led to a significant reduction in phosphorylated AKT levels in NCI-H460 cells; however, this was not noted in the other two cell lines. Gefitinib 42-51 AKT serine/threonine kinase 1 Homo sapiens 101-104 23200321-10 2013 In resistant cell lines harboring PIK3CA mutations, a PI3K inhibitor, LY294002, or AKT siRNA reduced cell viability with an additive effect demonstrated in combination with gefitinib. Gefitinib 173-182 AKT serine/threonine kinase 1 Homo sapiens 83-86 23200321-12 2013 Taken together this suggests that constitutively active AKT is a mechanism of intrinsic gefitinib resistance in SCCHN. Gefitinib 88-97 AKT serine/threonine kinase 1 Homo sapiens 56-59 23601074-3 2013 Here, we report that combinatorial treatment using EGFRis, such as gefitinib or erlotinib, with PI3K/AKT pathway inhibitors (PI3K/AKTis) demonstrated a synergistic, anti-proliferative effect in cell lines of the basal-like (BL) subtype, a subtype of TNBC. Gefitinib 67-76 AKT serine/threonine kinase 1 Homo sapiens 101-104 23601074-4 2013 Western blot analysis revealed that the gefitinib/PI-103 combination significantly reduced the level of both phospho-AKT and phospho-ERK in two susceptible BL subtype cell lines, SUM149PT and MDA-MB-468, whereas it had little or no effect on the level of phospho-ERK in two non-susceptible cell lines (HS578T and MDA-MB-231) of mesenchymal stem-like (MSL) TNBC subtype. Gefitinib 40-49 AKT serine/threonine kinase 1 Homo sapiens 117-120 23270470-2 2013 Gefitinib resistance is partly owing to the activation of two major downstream signaling pathways PI3K/AKT or MEK/ERK. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 103-106 23102728-6 2013 In the parental PC-9 cells, labeled as PC-9/wt, gefitinib completely inhibited EGF-induced phosphorylation of EGFR, AKT and ERK. Gefitinib 48-57 AKT serine/threonine kinase 1 Homo sapiens 116-119 23344263-9 2013 Inhibition of EGFR-ERK/AKT by gefitinib activates FOXO3a, which in turn reduces reactive oxygen species (ROS) and ROS-mediated CID. Gefitinib 30-39 AKT serine/threonine kinase 1 Homo sapiens 23-26 22941374-10 2012 Additionally, in gefitinib-resistant cell lines, the combination of gefitinib and everolimus not only showed stronger inhibition of phosphorylated mTOR and phosphorylated p70S6K expression than either drug alone but also reduced the levels of p-Akt and p-MAPK in both cell lines. Gefitinib 68-77 AKT serine/threonine kinase 1 Homo sapiens 245-248 23714663-10 2013 Western-blotting showed that compared with the control group, the expression of phosphorylated Akt and phospho-p38 proteins in PC-9 cells of the SB203580 + gefitinib group was almost completely suppressed. Gefitinib 156-165 AKT serine/threonine kinase 1 Homo sapiens 95-98 22922893-0 2012 Inhibition of the AKT/mTOR and erbB pathways by gefitinib, perifosine and analogs of gonadotropin-releasing hormone I and II to overcome tamoxifen resistance in breast cancer cells. Gefitinib 48-57 AKT serine/threonine kinase 1 Homo sapiens 18-21 22923287-8 2012 Furthermore, individual or combined treatment with EGCG and gefitinib suppressed the protein expression of p-EGFR and the phosphorylated protein levels of ERK, JNK, p38 and AKT and displayed inhibitory effects on metastatic ability of CAL-27 cells. Gefitinib 60-69 AKT serine/threonine kinase 1 Homo sapiens 173-176 22317763-8 2012 In the in vivo model, E7050 plus gefitinib resulted in marked regression of tumor growth associated with inhibition of Akt phosphorylation in cancer cells. Gefitinib 33-42 AKT serine/threonine kinase 1 Homo sapiens 119-122 22414764-12 2012 These enhanced autocrine/paracrine loops led to the constitutive activation of ERK and AKT and conferred increased sensitivity to gefitinib. Gefitinib 130-139 AKT serine/threonine kinase 1 Homo sapiens 87-90 21959795-7 2012 In addition, the gefitinib treated cells displayed increased levels of phosphorylation in IGF-1R and Akt, indicating the intensified activation of this cancer-associated signaling pathway. Gefitinib 17-26 AKT serine/threonine kinase 1 Homo sapiens 101-104 22313686-3 2012 Gefitinib significantly inhibited the cisplatin-induced ERK and Akt activation in Caov-3 and RMG-1 cells but not in A2780 cells. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 64-67 21544845-9 2012 Furthermore, pretreatment with gefitinib and the pharmacological inhibitors of PI3K (LY294002) and ERK1/2 (PD98059) prevented cigarette smoke-mediated Akt and ERK1/2 phosphorylation responses, HIF-1alpha production, HIF-1 activity and MUC5AC expression. Gefitinib 31-40 AKT serine/threonine kinase 1 Homo sapiens 151-154 22780923-10 2012 CONCLUSIONS: Gefitinib can reduce the migration capacity of triple-negative breast cancer cells through inhibiting phosphorylation of EGFR/PI3K/Akt pathway, suppressing the cell skeleton (microfilaments) remolding and changes of its polarization. Gefitinib 13-22 AKT serine/threonine kinase 1 Homo sapiens 144-147 22315058-0 2012 Acquisition of EMT phenotype in the gefitinib-resistant cells of a head and neck squamous cell carcinoma cell line through Akt/GSK-3beta/snail signalling pathway. Gefitinib 36-45 AKT serine/threonine kinase 1 Homo sapiens 123-126 22315058-9 2012 CONCLUSION: These results suggest that EMT in the gefitinib-resistant cells is mediated by the downregulation of EGFR and compensatory activation of Akt/GSK-3beta/snail pathway. Gefitinib 50-59 AKT serine/threonine kinase 1 Homo sapiens 149-152 22502680-0 2012 MicroRNA-214 regulates the acquired resistance to gefitinib via the PTEN/AKT pathway in EGFR-mutant cell lines. Gefitinib 50-59 AKT serine/threonine kinase 1 Homo sapiens 73-76 22502680-9 2012 Taken together, miR-214 may regulate the acquired resistance to gefitinib in HCC827 via PTEN/AKT signaling pathway. Gefitinib 64-73 AKT serine/threonine kinase 1 Homo sapiens 93-96 22977626-7 2011 The treatment of AG1024 combined with gefitinib resulted in a synergistic effect in inducing apoptosis, inhibiting cell proliferation and decreasing the expression of p-EGFR, p-Akt and p-ERK. Gefitinib 38-47 AKT serine/threonine kinase 1 Homo sapiens 177-180 22111840-8 2011 It is worth noting that the metabolism of gefitinib in the sensitive cells is a consequence and not the cause of drug responsiveness, indeed treatment with a CYP1A1 inhibitor increased the efficacy of the drug because it prevented the fall in intracellular gefitinib level and significantly enhanced the inhibition of EGFR autophosphorylation, MAPK and PI3K/AKT/mTOR signalling pathways and cell proliferation. Gefitinib 42-51 AKT serine/threonine kinase 1 Homo sapiens 358-361 21741919-13 2011 DARPP-32-mediated resistance to gefitinib resulted from increased phosphorylation of and interaction between EGFR and ERBB3, which led to phosphorylation of AKT (at serine 473). Gefitinib 32-41 AKT serine/threonine kinase 1 Homo sapiens 157-160 22057914-3 2012 We reported here that MK-2206, a potent allosteric Akt inhibitor currently in phase I trials in patients with solid tumors, could reinforce the cytocidal effect of gefitinib against glioma. Gefitinib 164-173 AKT serine/threonine kinase 1 Homo sapiens 51-54 21487020-0 2011 Nuclear translocation of epidermal growth factor receptor by Akt-dependent phosphorylation enhances breast cancer-resistant protein expression in gefitinib-resistant cells. Gefitinib 146-155 AKT serine/threonine kinase 1 Homo sapiens 61-64 21961726-10 2011 The activation of Akt was also inhibited by gefitinib, but only partly, suggesting a mechanism in addition to EGFR transactivation. Gefitinib 44-53 AKT serine/threonine kinase 1 Homo sapiens 18-21 21660955-8 2011 While gefitinib effectively abrogated phosphorylation of Akt- and mitogen-activated protein kinase in an EGFR TKI-sensitive cell line, phosphorylation of Akt persisted in two EGFR TKI-resistant cell lines, however, this phosphorylation was abrogated by lovastatin treatment. Gefitinib 6-15 AKT serine/threonine kinase 1 Homo sapiens 57-60 21878657-4 2011 In SCC-25 and Cal27 cells, gefitinib inhibited basal and EGF-stimulated EGFR, extracellular signal-regulated kinase (Erk), and Akt phosphorylation and reduced cell number. Gefitinib 27-36 AKT serine/threonine kinase 1 Homo sapiens 127-130 21961726-8 2011 In HT29 cells, in contrast, the EGFR tyrosine kinase inhibitor gefitinib blocked neurotensin-stimulated phosphorylation of both ERK and Akt, indicating transactivation of EGFR, independently of PKC. Gefitinib 63-72 AKT serine/threonine kinase 1 Homo sapiens 136-139 19946741-4 2010 Treatment with the gefitinib/trastuzumab combination produced, as compared with a single agent, a more prolonged blockade of AKT and MAPK activation, a more pronounced accumulation of cells in the G0/G1 phase of the cell cycle, a more significant increase in the levels of p27(kip1) and of hypophosphorylated pRb2, and a decrease in the levels of Cyclin D1 and survivin. Gefitinib 19-28 AKT serine/threonine kinase 1 Homo sapiens 125-128 21479670-6 2011 Increased insulin-like growth factor II expression induced by gefitinib or heterodimerization of EGFR and IGFR-1beta may trigger IGFR-1beta signal transduction via activation of Akt and MAPK. Gefitinib 62-71 AKT serine/threonine kinase 1 Homo sapiens 178-181 21220474-9 2011 In vitro experiments by considering short half-life of PI-103 reveal that transient exposure of PI-103 combined with gefitinib caused sustained inhibition of Akt phosphorylation, but not ERK1/2 phosphorylation, resulting in induction of tumor cell apoptosis even in the presence of HGF. Gefitinib 117-126 AKT serine/threonine kinase 1 Homo sapiens 158-161 21220474-10 2011 CONCLUSIONS: These results indicate that transient blockade of PI3K/Akt pathway by PI-103 and gefitinib could overcome HGF-mediated resistance to EGFR-TKIs by inducing apoptosis in EGFR mutant lung cancer. Gefitinib 94-103 AKT serine/threonine kinase 1 Homo sapiens 68-71 21087080-6 2011 The activation of Akt and PLCgamma was abolished by inhibition of HER1 with Gefitinib (5 muM), whereas this had no effect on the activity of MAPK. Gefitinib 76-85 AKT serine/threonine kinase 1 Homo sapiens 18-21 20716641-7 2010 TAK-701, a humanized monoclonal antibody to HGF, in combination with gefitinib inhibited the phosphorylation of MET, EGFR, extracellular signal-regulated kinase, and AKT in HCC827-HGF cells, resulting in suppression of cell growth and indicating that autocrine HGF-MET signaling contributes to gefitinib resistance in these cells. Gefitinib 69-78 AKT serine/threonine kinase 1 Homo sapiens 166-169 22037177-0 2011 Blocking the PI3K/AKT and MEK/ERK signaling pathways can overcome gefitinib-resistance in non-small cell lung cancer cell lines. Gefitinib 66-75 AKT serine/threonine kinase 1 Homo sapiens 18-21 22016830-9 2011 Thus, it appears that N-cadherin maintains the survival of the gefitinib-resistant lung cancer cells via the PI-3 kinase/Akt survival pathway. Gefitinib 63-72 AKT serine/threonine kinase 1 Homo sapiens 121-124 21655094-5 2011 Here, we first report that gefitinib or erlotinib can induce a high level of autophagy, which was accompanied by the inhibition of the PI3K/Akt/mTOR signaling pathway. Gefitinib 27-36 AKT serine/threonine kinase 1 Homo sapiens 140-143 19760159-10 2010 The combination of lovastatin and gefitinib effectively down-regulated RAS protein and suppressed the phosphorylation of RAF, ERK1/2, AKT, and EGFR in both cell lines. Gefitinib 34-43 AKT serine/threonine kinase 1 Homo sapiens 134-137 20444542-11 2010 Inhibition of PI3K/Akt signaling pathway restored sensitivity to gefitinib in HCC827-CR cells. Gefitinib 65-74 AKT serine/threonine kinase 1 Homo sapiens 19-22 20444542-12 2010 Taken together, these data show that PTEN instability-mediated constitutive Akt activation is involved in acquired resistance mechanisms to cetuximab and also induces de novo resistance to gefitinib. Gefitinib 189-198 AKT serine/threonine kinase 1 Homo sapiens 76-79 19921194-8 2010 Phosphatase and tensin homolog loss and sustained phosphorylation of Akt in spite of treatment with gefitinib were evident only in H1650 cells. Gefitinib 100-109 AKT serine/threonine kinase 1 Homo sapiens 69-72 19483462-7 2009 Pretreatment with gefitinib inhibits EGF-induced stimulation of both EGFR and downstream Akt and MAPK more efficiently in MCF-7/CAV1 than in MCF-7 cells. Gefitinib 18-27 AKT serine/threonine kinase 1 Homo sapiens 89-92 20097187-4 2010 H460 and A549 cells with EGFR receptor-independent over-activation of protein kinase B (Akt) or extracellular signal-regulated kinases (ERK) are significantly resistant to gefitinib. Gefitinib 172-181 AKT serine/threonine kinase 1 Homo sapiens 88-91 20159991-0 2010 Association of polymorphisms in AKT1 and EGFR with clinical outcome and toxicity in non-small cell lung cancer patients treated with gefitinib. Gefitinib 133-142 AKT serine/threonine kinase 1 Homo sapiens 32-36 20159991-6 2010 AKT1-SNP4 association with survival was also evaluated in 127 chemotherapy-treated/gefitinib-naive patients, whereas its relationship with AKT1 expression and gefitinib cytotoxicity was studied in 15 NSCLC cell lines. Gefitinib 83-92 AKT serine/threonine kinase 1 Homo sapiens 0-4 20159991-8 2010 Multivariate analyses and comparison with the gefitinib-nontreated population underlined its predictive significance, whereas the in vitro studies showed the association of lower AKT1 mRNA levels with gefitinib resistance. Gefitinib 201-210 AKT serine/threonine kinase 1 Homo sapiens 179-183 19956829-11 2010 Ex vivo culture with gefitinib resulted in distinct response patterns representing various states of activity of the ERK and AKT pathways. Gefitinib 21-30 AKT serine/threonine kinase 1 Homo sapiens 125-128 19898796-9 2009 We also demonstrated that gefitinib downregulates the activation of Akt and subsequent hTERT phosphorylation and translocation into the nucleus in MDA-MB-231 cells. Gefitinib 26-35 AKT serine/threonine kinase 1 Homo sapiens 68-71 19706799-7 2009 However, its combination with gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, induced supra-additive effects in all cell lines that were associated with cell cycle blockage and inhibition of AKT phosphorylation. Gefitinib 30-39 AKT serine/threonine kinase 1 Homo sapiens 208-211 20651347-16 2010 In PTEN-negative Ishikawa cells, OHT in combination with any drug had no effects, but inhibition of the PI3K/AKT/mTOR pathway by everolimus in combination with gefitinib showed synergistic effects. Gefitinib 160-169 AKT serine/threonine kinase 1 Homo sapiens 109-112 19756373-7 2010 Gefitinib at IC(50) concentrations significantly suppressed EGF-induced activation of p-EGFR, phospho-mitogen-activated protein kinase (p-MAPK) and p-STAT3, but p-AKT showed persistent activation in HK1 and HONE-1 cells. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 163-166 19922467-6 2010 Gefitinib has been shown to inhibit cell survival and growth signaling pathways such as the extracellular signal-regulated kinase 1/2 pathway and the Akt pathway, as a consequence of the inactivation of EGFR. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 150-153 19371940-0 2009 Activated Akt prevents antitumor activity of gefitinib in renal cancer cells. Gefitinib 45-54 AKT serine/threonine kinase 1 Homo sapiens 10-13 19371940-4 2009 The changes in signaling cascades and cell survival that were induced by gefitinib in combination with either the phosphatidylinositol 3-kinase inhibitor LY294002 or the knockdown of Akt expression by transient transfection with Akt small interfering RNA were examined in 786-O cells. Gefitinib 73-82 AKT serine/threonine kinase 1 Homo sapiens 183-186 19371940-4 2009 The changes in signaling cascades and cell survival that were induced by gefitinib in combination with either the phosphatidylinositol 3-kinase inhibitor LY294002 or the knockdown of Akt expression by transient transfection with Akt small interfering RNA were examined in 786-O cells. Gefitinib 73-82 AKT serine/threonine kinase 1 Homo sapiens 229-232 19371940-6 2009 Although in each line, the phosphorylation of EGFR and extracellular signal-regulated kinase was inhibited by 0.1 muM gefitinib, the phosphorylation of Akt was constitutive and was not inhibited by even 10 muM gefitinib. Gefitinib 118-127 AKT serine/threonine kinase 1 Homo sapiens 152-155 19371940-7 2009 In 786-O cells, the phosphorylation of both extracellular signal-regulated kinase and Akt was inhibited by gefitinib used in combination with either LY294002 or the knockdown of Akt expression, and the viability of 786-O cells was suppressed significantly by gefitinib used in combination with LY294002 (P < .0001) or Akt small interfering RNA (P = .0044). Gefitinib 107-116 AKT serine/threonine kinase 1 Homo sapiens 86-89 19371940-7 2009 In 786-O cells, the phosphorylation of both extracellular signal-regulated kinase and Akt was inhibited by gefitinib used in combination with either LY294002 or the knockdown of Akt expression, and the viability of 786-O cells was suppressed significantly by gefitinib used in combination with LY294002 (P < .0001) or Akt small interfering RNA (P = .0044). Gefitinib 107-116 AKT serine/threonine kinase 1 Homo sapiens 178-181 19371940-7 2009 In 786-O cells, the phosphorylation of both extracellular signal-regulated kinase and Akt was inhibited by gefitinib used in combination with either LY294002 or the knockdown of Akt expression, and the viability of 786-O cells was suppressed significantly by gefitinib used in combination with LY294002 (P < .0001) or Akt small interfering RNA (P = .0044). Gefitinib 107-116 AKT serine/threonine kinase 1 Homo sapiens 178-181 19371940-7 2009 In 786-O cells, the phosphorylation of both extracellular signal-regulated kinase and Akt was inhibited by gefitinib used in combination with either LY294002 or the knockdown of Akt expression, and the viability of 786-O cells was suppressed significantly by gefitinib used in combination with LY294002 (P < .0001) or Akt small interfering RNA (P = .0044). Gefitinib 259-268 AKT serine/threonine kinase 1 Homo sapiens 86-89 19371940-8 2009 CONCLUSIONS: Constitutively activated Akt might prevent the antitumor efficacy of gefitinib in renal cell carcinoma, and the therapeutic effectiveness of gefitinib might be improved by inhibiting Akt activation. Gefitinib 82-91 AKT serine/threonine kinase 1 Homo sapiens 38-41 19371940-8 2009 CONCLUSIONS: Constitutively activated Akt might prevent the antitumor efficacy of gefitinib in renal cell carcinoma, and the therapeutic effectiveness of gefitinib might be improved by inhibiting Akt activation. Gefitinib 154-163 AKT serine/threonine kinase 1 Homo sapiens 196-199 19233551-6 2009 Gefitinib suppressed EGF-activated phosphorylation of ERK1/2 and Akt, while zoledronate seemed to impose its pharmacological effect independent of ERK1/2 and Akt phosphorylation. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 65-68 19318229-5 2009 ZD6474 and ZD1839 inhibited EGF-induced phosphorylation of EGFR, AKT and ERK, whereas VEGF-induced phosphorylation of VEGFR2 was completely inhibited with 0.1 microM SU11248. Gefitinib 11-17 AKT serine/threonine kinase 1 Homo sapiens 65-68 19033425-7 2009 Phosphorylated AKT inhibition paralleled that of phosphorylated EGFR, suggesting the presence of an autocrine gefitinib-sensitive EGFR/AKT pathway. Gefitinib 110-119 AKT serine/threonine kinase 1 Homo sapiens 15-18 19033425-7 2009 Phosphorylated AKT inhibition paralleled that of phosphorylated EGFR, suggesting the presence of an autocrine gefitinib-sensitive EGFR/AKT pathway. Gefitinib 110-119 AKT serine/threonine kinase 1 Homo sapiens 135-138 17902048-7 2008 Furthermore, gefitinib significantly enhances IGF-II-mediated phosphorylation of IRS-1 Y612 and AKT in Tam-R cells. Gefitinib 13-22 AKT serine/threonine kinase 1 Homo sapiens 96-99 19414346-5 2009 RESULTS: BCRP reduced intracellular gefitinib levels and attenuated inhibitory activities of gefitinib to EGF-dependent EGFR signalings including downstream MAPK and Akt pathways in gefitinib-sensitive PC-9 cells. Gefitinib 93-102 AKT serine/threonine kinase 1 Homo sapiens 166-169 19414346-5 2009 RESULTS: BCRP reduced intracellular gefitinib levels and attenuated inhibitory activities of gefitinib to EGF-dependent EGFR signalings including downstream MAPK and Akt pathways in gefitinib-sensitive PC-9 cells. Gefitinib 93-102 AKT serine/threonine kinase 1 Homo sapiens 166-169 18803287-6 2008 Gefitinib fully inhibited EGF-induced and constitutive Akt activation only in chemoresistant cells. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 55-58 18803287-11 2008 Our study indicates that in chemoresistant cells gefitinib inhibits both an enhanced EGF-triggered pathway and a constitutive HER3-mediated Akt activation, indicating that inhibition of HER3 together with that of EGFR could be relevant in chemorefractory tumors. Gefitinib 49-58 AKT serine/threonine kinase 1 Homo sapiens 140-143 18566746-6 2008 For example, combining gefitinib with inhibitors of the PI3K/AKT pathway show enhanced cytotoxicity in glioblastoma derived cell lines. Gefitinib 23-32 AKT serine/threonine kinase 1 Homo sapiens 61-64 19150933-10 2009 Response to gefitinib was associated with reduced phosphorylation of both mitogen activated protein kinase (MAPK) and Akt and induction of G(1) arrest. Gefitinib 12-21 AKT serine/threonine kinase 1 Homo sapiens 118-121 19318490-6 2009 RESULTS: In vitro, gefitinib inhibited cell proliferation with differing IC(50), and suppressed activation of EGFR and downstream signaling molecules protein kinase B (AKT), extracellular signal-regulated kinase 1/2, signal transducer and activator of transcription 3 (STAT3), and nuclear factor kappaB. Gefitinib 19-28 AKT serine/threonine kinase 1 Homo sapiens 168-171 19318490-9 2009 CONCLUSIONS: Gefitinib sensitivity is correlated with p-AKT and p-STAT3 activation in HNSCC cell lines and tumor specimens. Gefitinib 13-22 AKT serine/threonine kinase 1 Homo sapiens 56-59 19212642-6 2009 The effect of gefitinib on down-regulation of HIF-1alpha was reversed by transfection of constitutively active form of Akt. Gefitinib 14-23 AKT serine/threonine kinase 1 Homo sapiens 119-122 19212642-10 2009 In conclusion, gefitinib was able to circumvent hypoxia-induced drug resistance suggesting that the effective suppression of HIF-1alpha by the inhibition of EGFR-Akt pathway may overcome the hypoxia-induced drug resistance. Gefitinib 15-24 AKT serine/threonine kinase 1 Homo sapiens 162-165 18060492-4 2008 The phosphorylation of EGFR, ErbB-2, ErbB-3 and Akt was significantly reduced in gefitinib-resistant cells. Gefitinib 81-90 AKT serine/threonine kinase 1 Homo sapiens 48-51 18506376-3 2008 Gefitinib IC50 values ranged between 0.064 and 33 microM, its capability to induce apoptosis and cell accumulation in G0/G1 phase was cell line-specific, and the main EGFR-related pathway involved in gefitinib activity was PI3K/Akt/mTor. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 228-231 18407408-5 2008 Inhibition of phosphorylation of EGFR, Akt, and Erk by gefitinib was detected using Western blotting, and cell inhibition tests were conducted to evaluate the bio-behavior. Gefitinib 55-64 AKT serine/threonine kinase 1 Homo sapiens 39-42 18407408-6 2008 Gefitinib inhibited the phosphorylation of EGFR, Akt, and Erk to a greater degree in exon 19 deletion cells than in L858R cells. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 49-52 18386816-7 2008 Tumor regression was associated with inhibition of AKT and MAPK pathways by gefitinib. Gefitinib 76-85 AKT serine/threonine kinase 1 Homo sapiens 51-54 18413750-0 2008 Targeting endoplasmic reticulum stress and Akt with OSU-03012 and gefitinib or erlotinib to overcome resistance to epidermal growth factor receptor inhibitors. Gefitinib 66-75 AKT serine/threonine kinase 1 Homo sapiens 43-46 17982658-8 2007 Phosphorylated Akt, which seems to be involved in the gefitinib resistance of this subpopulation, did not change after gemcitabine exposure. Gefitinib 54-63 AKT serine/threonine kinase 1 Homo sapiens 15-18 18347153-8 2008 Gefitinib was more effective in inhibiting ERK1/2 and Akt phosphorylation in IGROV-1 cells than in IGROV-1/OHP and IGROV-1/Pt1 cells. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 54-57 18172786-6 2008 In western blot analysis, ZD1839 single agent inhibited the activation of EGFR and downstream cell signal transduction AKT and extrocellular signal-regulated kinase (ERK) pathways, the transcription activity of nuclear factor-kappa B (NF-kappaB), and the expression of COX-2. Gefitinib 26-32 AKT serine/threonine kinase 1 Homo sapiens 119-122 17910952-4 2008 Distinct differences in the pathways leading to phosphorylation and activation of Akt from stimulated beta1 integrins and EGF receptor were observed, including opposing sensitivity to the tyrosine kinase inhibitors PP2 and Gefitinib. Gefitinib 223-232 AKT serine/threonine kinase 1 Homo sapiens 82-85 18089711-5 2007 In the sensitive cells, gefitinib treatment causes cell cycle arrest predominantly at the G(0)-G(1) phase and apoptosis, which is associated with FOXO3a dephosphorylation at Akt sites and nuclear translocation, whereas in the resistant cells, FOXO3a stays phosphorylated and remains in the cytoplasm. Gefitinib 24-33 AKT serine/threonine kinase 1 Homo sapiens 174-177 17150102-0 2006 Gefitinib (IRESSA) sensitive lung cancer cell lines show phosphorylation of Akt without ligand stimulation. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 76-79 17975165-10 2007 Responders showed a nonstatistically significant trend toward a more pronounced reduction in the expression of p-EGFR, p-MAPK, and p-AKT after gefitinib treatment. Gefitinib 143-152 AKT serine/threonine kinase 1 Homo sapiens 133-136 17699786-5 2007 In keeping with the proposed role of T790M in abrogating gefitinib binding with EGFR, gefitinib-treated RPC-9 hardly displayed any decrease in the constitutive phosphorylation of EGFR, Akt, or Erk1/2 unlike in PC-9 cells. Gefitinib 86-95 AKT serine/threonine kinase 1 Homo sapiens 185-188 17237287-4 2007 Gefitinib also inhibited baseline EGFR, AKT, and extracellular signal-regulated kinase (ERK) phosphorylation in the EGFR-dependent cells maintained in serum-free medium, whereas it had no effect on baseline EGFR or ERK phosphorylation in the EGFR-independent cells. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 40-43 17577220-1 2007 BACKGROUND: Preclinical studies have demonstrated that the inhibition of the PI3K/Akt/mTOR pathway restores gefitinib sensitivity in resistant cancer cell lines. Gefitinib 108-117 AKT serine/threonine kinase 1 Homo sapiens 82-85 17616694-7 2007 ZD4054 plus gefitinib resulted in a greater inhibition of EGFR, MAPK, and AKT phosphorylation, indicating the critical role of these interconnected signaling proteins. Gefitinib 12-21 AKT serine/threonine kinase 1 Homo sapiens 74-77 17538169-0 2007 Prospective study of gefitinib in epidermal growth factor receptor fluorescence in situ hybridization-positive/phospho-Akt-positive or never smoker patients with advanced non-small-cell lung cancer: the ONCOBELL trial. Gefitinib 21-30 AKT serine/threonine kinase 1 Homo sapiens 119-122 17505004-9 2007 One of the underlying mechanisms for augmentation of docetaxel-induced apoptosis by celecoxib and ZD1839 is to further inhibit the activation of prosurvival pathway molecules, such as extracellular signal-regulated kinase and AKT, and the promotion of aberrant apoptosis. Gefitinib 98-104 AKT serine/threonine kinase 1 Homo sapiens 226-229 17004112-1 2007 AKT and MAPK signaling are involved in the resistance of breast cancer cells to the EGFR tyrosine kinase inhibitor gefitinib. Gefitinib 115-124 AKT serine/threonine kinase 1 Homo sapiens 0-3 17513607-3 2007 ZD1839 has been shown to inhibit cell cycle progression through inhibition of signaling pathways such as phosphatidylinositol 3"-kinase-Akt and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) cascades. Gefitinib 0-6 AKT serine/threonine kinase 1 Homo sapiens 136-139 17349623-8 2007 Pretreatment of NSCLC cells with GRP resulted in an increase in the IC(50) of gefitinib of up to 9-fold; this protective effect was mimicked by the pretreatment of cells with amphiregulin and reversed by Akt or PI3K inhibition. Gefitinib 78-87 AKT serine/threonine kinase 1 Homo sapiens 204-207 17205515-8 2007 The effect of gefitinib treatment on the activity of extra cellular-regulated kinase (Erk), Akt, JNK and p38 kinases was assessed in IC9LC11 and IC1LC131, two NSCLC xenografts selected for their sensitivity and resistance to gefitinib, respectively. Gefitinib 14-23 AKT serine/threonine kinase 1 Homo sapiens 92-95 17205515-9 2007 In IC9LC11, gefitinib strongly inhibited Erk, Akt and Jnk phosphorylation, but P38 remained active. Gefitinib 12-21 AKT serine/threonine kinase 1 Homo sapiens 46-49 17270025-5 2007 Consistently, phospho-Akt levels were decreased in response to gefitinib in cells expressing EGFR-L858R but not in cells with EGFR-WT. Gefitinib 63-72 AKT serine/threonine kinase 1 Homo sapiens 22-25 17270025-8 2007 The activated K-Ras inhibited the effects of gefitinib treatment on cell growth, cell death induction and levels of phospho-Akt, as well as phospho-Erk. Gefitinib 45-54 AKT serine/threonine kinase 1 Homo sapiens 124-127 17308080-0 2007 Gefitinib reverses TRAIL resistance in human bladder cancer cell lines via inhibition of AKT-mediated X-linked inhibitor of apoptosis protein expression. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 89-92 17317832-1 2007 PURPOSE: In preclinical models, calcitriol and the tyrosine kinase inhibitor gefitinib are synergistic and modulate extracellular signal-regulated kinase (Erk) and Akt pathways. Gefitinib 77-86 AKT serine/threonine kinase 1 Homo sapiens 164-167 17317832-14 2007 Gefitinib treatment inhibited EGFR, Akt, and Erk phosphorylation in the skin. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 36-39 17686159-7 2007 Gefitinib prevented HRGbeta1-driven erbB3/EGFR heterodimerization, ERK1/2 activation and Tam-R cell proliferation, but HRGbeta1-driven erbB3/erbB2 heterodimerization, AKT activation and Tam-R cell invasion were maintained. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 167-170 17686159-11 2007 CONCLUSION: HRGbeta1 can overcome the inhibitory effects of gefitinib on cell growth and invasion in Tam-R cells through promotion of erbB3/erbB2 heterodimerization and activation of the phosphatidylinositol 3-kinase/AKT signalling pathway. Gefitinib 60-69 AKT serine/threonine kinase 1 Homo sapiens 217-220 17189395-7 2006 This review also describes a possible association between EGFR phosphorylation and drug sensitivity in cancer cells, as well as discussing the antiangiogenic effect of gefitinib in association with EGFR activation and phosphatidylinositol 3-kinase/Akt activation in vascular endothelial cells. Gefitinib 168-177 AKT serine/threonine kinase 1 Homo sapiens 248-251 17150102-9 2006 Akt phosphorylation was partially inhibited by gefitinib in all sensitive cell lines. Gefitinib 47-56 AKT serine/threonine kinase 1 Homo sapiens 0-3 17150102-10 2006 CONCLUSION: These results suggest that Akt phosphorylation without ligand stimulation may play a key signaling role in gefitinib sensitivity, especially intermediate-sensitivity. Gefitinib 119-128 AKT serine/threonine kinase 1 Homo sapiens 39-42 16532343-6 2006 Upon gefitinib treatment, EGFR activation and subsequent downstream activation through Erk and Akt were significantly inhibited in HAG-1 cells. Gefitinib 5-14 AKT serine/threonine kinase 1 Homo sapiens 95-98 17088902-8 2006 These results suggest that the antitumour effect of gefitinib is due to the effective inhibition of HER2-driven constitutive activation of phosphatidylinositol-3-kinase (PI3K)/Akt pathway, and that the acquired resistance to gefitinib is due to the constitutive activation of Ras/MAPK pathway in compensation for PI3K/Akt pathway. Gefitinib 52-61 AKT serine/threonine kinase 1 Homo sapiens 176-179 17088902-8 2006 These results suggest that the antitumour effect of gefitinib is due to the effective inhibition of HER2-driven constitutive activation of phosphatidylinositol-3-kinase (PI3K)/Akt pathway, and that the acquired resistance to gefitinib is due to the constitutive activation of Ras/MAPK pathway in compensation for PI3K/Akt pathway. Gefitinib 52-61 AKT serine/threonine kinase 1 Homo sapiens 318-321 16532343-9 2006 CONCLUSION: Our results suggest that activated Ras and Src could induce gefitinib resistance by activating either or both of Akt and Erk signaling pathways, thus providing a strategic rationale for assessment of these specific signaling molecules downstream of EGFR to customize treatment. Gefitinib 72-81 AKT serine/threonine kinase 1 Homo sapiens 125-128 17186707-6 2006 Experimentally it is confirmed that impaired internalisation of ErbB1 is associated with increased AKT activity, which can be blocked by gefitinib. Gefitinib 137-146 AKT serine/threonine kinase 1 Homo sapiens 99-102 17186707-7 2006 On the basis of these experimental and computational results, it is surmised that gefitinib sensitivity is a marker of a reliance on AKT signalling for cell survival that may be brought about by impaired ErbB1 internalisation. Gefitinib 82-91 AKT serine/threonine kinase 1 Homo sapiens 133-136 16906227-5 2006 In gefitinib-sensitive lung cancer cells with EGFR mutations and amplifications, exogenous introduction of EGFR T790M effectively conferred resistance to gefitinib and continued ErbB-3/PI3K/Akt signaling when in cis to an activating mutation. Gefitinib 3-12 AKT serine/threonine kinase 1 Homo sapiens 190-193 17018616-3 2006 The recruitment of the HER2/Vav2/Rac1/Pak1/actin/actinin complex to lamellipodia was abrogated by actinin siRNAs, dominant-negative (dn) p85, gefitinib, and dn-Rac1 or dn-Pak1, suggesting that the reciprocal interplay of PI3K, HER2 kinase, and Rac GTPases with the actin cytoskeleton is necessary for TGF-beta action in oncogene-overexpressing cells. Gefitinib 142-151 AKT serine/threonine kinase 1 Homo sapiens 33-36 16441427-0 2006 Activation of MEK/ERK and PI3K/Akt pathways by fibronectin requires integrin alphav-mediated ADAM activity in hepatocellular carcinoma: a novel functional target for gefitinib. Gefitinib 166-175 AKT serine/threonine kinase 1 Homo sapiens 31-34 16731747-7 2006 Two of nine EGFR wild type and one of two EGFR mutant NSCLC cells were sensitive to gefitinib, and this was associated with a decrease in phospho (p)-Akt and pErk1/2 following gefitinib exposure. Gefitinib 84-93 AKT serine/threonine kinase 1 Homo sapiens 150-153 16585207-6 2006 Exposure to gefitinib or a small interfering RNA construct specific for TGF-alpha reversed the constitutive EGFR phosphorylation and downstream target [extracellular signal-regulated kinases (ERK), AKT] phosphorylation in the gefitinib-sensitive cells but had no effects on ERK or AKT phosphorylation in gefitinib-resistant cells. Gefitinib 12-21 AKT serine/threonine kinase 1 Homo sapiens 198-201 16585207-6 2006 Exposure to gefitinib or a small interfering RNA construct specific for TGF-alpha reversed the constitutive EGFR phosphorylation and downstream target [extracellular signal-regulated kinases (ERK), AKT] phosphorylation in the gefitinib-sensitive cells but had no effects on ERK or AKT phosphorylation in gefitinib-resistant cells. Gefitinib 12-21 AKT serine/threonine kinase 1 Homo sapiens 281-284 16540671-7 2006 These effects of gefitinib on VEGF promoter activity and DNA binding were both reversed by Akt expression. Gefitinib 17-26 AKT serine/threonine kinase 1 Homo sapiens 91-94 16675591-0 2006 Gefitinib inhibits the growth and invasion of urothelial carcinoma cell lines in which Akt and MAPK activation is dependent on constitutive epidermal growth factor receptor activation. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 87-90 16675591-2 2006 The objective of this study was to evaluate the effects of the specific EGFR tyrosine kinase inhibitor gefitinib on activation of the Akt and mitogen-activated protein kinase (MAPK) pathways in human urothelial cell carcinoma (UCC) cell lines and to identify potential markers of gefitinib responsiveness in biopsy samples of UCC. Gefitinib 103-112 AKT serine/threonine kinase 1 Homo sapiens 134-137 16675591-9 2006 These effects did not depend on the level of expression of EGFR but they were associated with the down-regulation of MAPK and Akt activity; in 1207 cells, gefitinib activity was associated with p27 up-regulation and p21 and matrix metalloproteinase-9 down-regulation. Gefitinib 155-164 AKT serine/threonine kinase 1 Homo sapiens 126-129 16675591-11 2006 CONCLUSIONS: Activation of EGFR, Akt, and MAPK defines a subset of UCC which might provide information for the identification of gefitinib responders. Gefitinib 129-138 AKT serine/threonine kinase 1 Homo sapiens 33-36 16419029-3 2006 Although treatment with gefitinib inhibited EGFR activation in the three cell lines in a similar fashion, significant reduction of both p42/p44-MAPK and AKT phosphorylation was observed in SK-Br-3 and MDA-MB-361, but not in MDA-MB-468 cells. Gefitinib 24-33 AKT serine/threonine kinase 1 Homo sapiens 153-156 16638863-12 2006 In addition to EGFR mutation, K-ras mutation and Akt phosphorylation aid in better prediction of gefitinib responsiveness in non-small-cell lung cancer. Gefitinib 97-106 AKT serine/threonine kinase 1 Homo sapiens 49-52 16525641-7 2006 Treatment with either ZD1839 or LY294002 (the latter, a PI3K inhibitor) suppressed phosphorylation of AKT by Western blot. Gefitinib 22-28 AKT serine/threonine kinase 1 Homo sapiens 102-105 16229013-4 2006 Following 2-h treatment, gefitinib significantly inhibited EGFR autophosphorylation and subsequent downstream signaling pathway through Erk and Akt, and induced accumulation of cells in the G0/G1 phase of the cell cycle at 24-h, accompanied by a concomitant increase in p21 transcript and increased expression of p27. Gefitinib 25-34 AKT serine/threonine kinase 1 Homo sapiens 144-147 16373402-5 2006 When the 293(D) cells were exposed to gefitinib, an immunoblotting analysis revealed remarkable inhibition of AKT phosphorylation but not phospho-p44/42 MAPK. Gefitinib 38-47 AKT serine/threonine kinase 1 Homo sapiens 110-113 16373402-9 2006 Gefitinib-inhibited phospho-AKT predominantly in deletional EGFR expressing cells. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 28-31 16568376-8 2006 When the cells were co-treated with gefitinib and TGF-alpha, enhanced proliferation and activation of ERK1/2 and AKT were canceled, and the cell-cycle promotion by TGF-alpha was inhibited by co-treatment with gefitinib and TGF-alpha, independently of expression levels of EGFR. Gefitinib 36-45 AKT serine/threonine kinase 1 Homo sapiens 113-116 16568376-8 2006 When the cells were co-treated with gefitinib and TGF-alpha, enhanced proliferation and activation of ERK1/2 and AKT were canceled, and the cell-cycle promotion by TGF-alpha was inhibited by co-treatment with gefitinib and TGF-alpha, independently of expression levels of EGFR. Gefitinib 209-218 AKT serine/threonine kinase 1 Homo sapiens 113-116 16003751-5 2006 Gefitinib effectively blocked Akt and Erk phosphorylation in two gefitinib-sensitive NSCLC cell lines, further supporting our previous findings that persistent activity of the PI3K/Akt and/or Ras/Erk pathways is associated with gefitinib-resistance of NSCLC cell lines. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 30-33 16003751-5 2006 Gefitinib effectively blocked Akt and Erk phosphorylation in two gefitinib-sensitive NSCLC cell lines, further supporting our previous findings that persistent activity of the PI3K/Akt and/or Ras/Erk pathways is associated with gefitinib-resistance of NSCLC cell lines. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 181-184 16003751-6 2006 Gefitinib-resistant NSCLC cell lines, showing EGFR-independent activity of the PI3K/Akt or Ras/Erk pathways, were treated with gefitinib in combination with specific inhibitors of mTOR, P13K, Ras, and MEK. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 84-87 16003751-8 2006 These data suggest that combination treatment of NSCLC cells with gefitinib and specific inhibitors of the PI3K/Akt and Ras/Erk pathways may provide a successful strategy. Gefitinib 66-75 AKT serine/threonine kinase 1 Homo sapiens 112-115 16322337-4 2005 We reported that the EGFR-selective tyrosine kinase inhibitor gefitinib (ZD1839; Iressa) is able to induce growth inhibition, G(1) arrest and apoptosis in PCa cells and that its effectiveness is associated primarily with phosphatase and tensin homologue deleted from chromosome 10 (PTEN) expression (and thus Akt activity). Gefitinib 62-71 AKT serine/threonine kinase 1 Homo sapiens 309-312 16322337-4 2005 We reported that the EGFR-selective tyrosine kinase inhibitor gefitinib (ZD1839; Iressa) is able to induce growth inhibition, G(1) arrest and apoptosis in PCa cells and that its effectiveness is associated primarily with phosphatase and tensin homologue deleted from chromosome 10 (PTEN) expression (and thus Akt activity). Gefitinib 73-79 AKT serine/threonine kinase 1 Homo sapiens 309-312 16322337-8 2005 Thus the effectiveness of gefitinib requires growth factor receptor-stimulated PI3K/Akt and MAPK signalling to be intact and functional. Gefitinib 26-35 AKT serine/threonine kinase 1 Homo sapiens 84-87 16373711-4 2005 The presence of a functional EGFR pathway sensitive to gefitinib was shown in HMME7 cells (gefitinib-induced decrease in phospho-EGFR, phospho-p42/p44, and phospho-Akt). Gefitinib 91-100 AKT serine/threonine kinase 1 Homo sapiens 164-167 16009452-6 2005 Gefitinib also inhibited the phosphorylation of MAPK and Akt, and the selective inhibitors PD98059 and LY294002 also suppressed MUC5AC protein synthesis. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 57-60 16373711-4 2005 The presence of a functional EGFR pathway sensitive to gefitinib was shown in HMME7 cells (gefitinib-induced decrease in phospho-EGFR, phospho-p42/p44, and phospho-Akt). Gefitinib 55-64 AKT serine/threonine kinase 1 Homo sapiens 164-167 16009452-7 2005 These findings suggest that gefitinib may inhibits MUC5AC synthesis, at least in part, through MAPK and Akt signaling pathways. Gefitinib 28-37 AKT serine/threonine kinase 1 Homo sapiens 104-107 15761868-14 2005 Expression of phosphorylated AKT was increased in PC-9 cells and inhibited by 0.02 microM gefitinib. Gefitinib 90-99 AKT serine/threonine kinase 1 Homo sapiens 29-32 15761868-16 2005 These results suggest that alterations of adaptor-protein-mediated signal transduction from EGFR to AKT is a possible mechanism of the resistance to gefitinib in PC-9/ZD cells. Gefitinib 149-158 AKT serine/threonine kinase 1 Homo sapiens 100-103 16023108-7 2005 ZD1839 inhibited the phosphorylation of Akt, and enhanced TRAIL-induced apoptosis via activation of caspase-3 and caspase-9, and inactivation of Bcl-xL. Gefitinib 0-6 AKT serine/threonine kinase 1 Homo sapiens 40-43 16106023-12 2005 Gefitinib treatment decreased EGFR, ERK1/2, and Akt phosphorylation in EGFR mutant cell lines whereas cetuximab had relatively little effect. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 48-51 15841081-5 2005 However, gefitinib inhibited the TNF-alpha-induced activation of MAPKs and Akt. Gefitinib 9-18 AKT serine/threonine kinase 1 Homo sapiens 75-78 15947117-6 2005 A significant reduction in the basal levels of activation of the EGFR and of Akt was observed in HDS cells following treatment with gefitinib. Gefitinib 132-141 AKT serine/threonine kinase 1 Homo sapiens 77-80 15788691-9 2005 Combining lovastatin and gefitinib treatments showed enhanced inhibition of AKT activation by EGF in SCC9 cells. Gefitinib 25-34 AKT serine/threonine kinase 1 Homo sapiens 76-79 15781651-6 2005 In addition, ZD1839 itself inhibited survival pathways by causing a partial dephosphorylation of Akt and a marked down-regulation of survivin. Gefitinib 13-19 AKT serine/threonine kinase 1 Homo sapiens 97-100 15731348-11 2005 We conclude that ErbB-3 is used to couple EGFR to the PI3K/Akt pathway in gefitinib-sensitive NSCLC cell lines harboring WT and mutant EGFRs. Gefitinib 74-83 AKT serine/threonine kinase 1 Homo sapiens 59-62 15731348-3 2005 In this study, we observe that gefitinib reduces phospho-Akt levels only in NSCLC cell lines in which it inhibits growth. Gefitinib 31-40 AKT serine/threonine kinase 1 Homo sapiens 57-60 15731348-6 2005 Gefitinib dissociates this complex, thereby linking EGFR inhibition to decreased Akt activity. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 81-84 15870831-5 2005 Gefitinib-resistant subpopulations demonstrated increased Akt phosphorylation (not inhibited by gefitinib), reduced PTEN protein expression and loss of the EGFR gene mutation when compared with parental cell lines. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 58-61 29793222-6 2004 Furthermore, it has been reported that the phosphatidylinositol 3-kinase/Akt signaling pathway plays a critical role in the antitumor effects of gefitinib. Gefitinib 145-154 AKT serine/threonine kinase 1 Homo sapiens 73-76 15258753-0 2004 Gefitinib ("IRESSA", ZD1839) inhibits EGF-induced invasion in prostate cancer cells by suppressing PI3 K/AKT activation. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 105-108 15492241-7 2004 Although EGFR and AKT are constitutively phosphorylated in H3255, H1666, and H441 cell lines, AKT is completely inhibited by gefitinib treatment only in the H3255 cell line. Gefitinib 125-134 AKT serine/threonine kinase 1 Homo sapiens 18-21 15492241-7 2004 Although EGFR and AKT are constitutively phosphorylated in H3255, H1666, and H441 cell lines, AKT is completely inhibited by gefitinib treatment only in the H3255 cell line. Gefitinib 125-134 AKT serine/threonine kinase 1 Homo sapiens 94-97 15258753-0 2004 Gefitinib ("IRESSA", ZD1839) inhibits EGF-induced invasion in prostate cancer cells by suppressing PI3 K/AKT activation. Gefitinib 21-27 AKT serine/threonine kinase 1 Homo sapiens 105-108 15258753-13 2004 In addition, we demonstrate here that gefitinib inhibits EGF-induced activation of PI3 K/AKT pathway in both cell lines. Gefitinib 38-47 AKT serine/threonine kinase 1 Homo sapiens 89-92 15258753-14 2004 CONCLUSION: Overall, our results demonstrate that gefitinib is able to suppress invasion and proliferation of AI-PC cells by suppressing EGF-stimulated activation of the PI3 K/AKT pathway and support a possible use of the drug in the treatment of advanced PC to limit not only proliferation but also invasion to other districts. Gefitinib 50-59 AKT serine/threonine kinase 1 Homo sapiens 176-179 15377841-6 2004 Akt phosphorylation is reduced by gefitinib ("Iressa"/ZD1839). Gefitinib 34-43 AKT serine/threonine kinase 1 Homo sapiens 0-3 15292385-3 2004 Because activation of these pathways is dependent on the phosphorylation status of the components, we evaluated the association between phosphorylation status of Akt (P-Akt) and MAPK (P-MAPK) and gefitinib activity in patients with advanced NSCLC. Gefitinib 196-205 AKT serine/threonine kinase 1 Homo sapiens 162-165 15292385-13 2004 CONCLUSIONS: Patients with P-Akt-positive tumors who received gefitinib had a better response rate, disease control rate, and time to progression than patients with P-Akt-negative tumors, suggesting that gefitinib may be most effective in patients with basal Akt activation. Gefitinib 62-71 AKT serine/threonine kinase 1 Homo sapiens 27-32 15292385-13 2004 CONCLUSIONS: Patients with P-Akt-positive tumors who received gefitinib had a better response rate, disease control rate, and time to progression than patients with P-Akt-negative tumors, suggesting that gefitinib may be most effective in patients with basal Akt activation. Gefitinib 62-71 AKT serine/threonine kinase 1 Homo sapiens 29-32 15292385-13 2004 CONCLUSIONS: Patients with P-Akt-positive tumors who received gefitinib had a better response rate, disease control rate, and time to progression than patients with P-Akt-negative tumors, suggesting that gefitinib may be most effective in patients with basal Akt activation. Gefitinib 204-213 AKT serine/threonine kinase 1 Homo sapiens 27-32 15292385-13 2004 CONCLUSIONS: Patients with P-Akt-positive tumors who received gefitinib had a better response rate, disease control rate, and time to progression than patients with P-Akt-negative tumors, suggesting that gefitinib may be most effective in patients with basal Akt activation. Gefitinib 204-213 AKT serine/threonine kinase 1 Homo sapiens 165-170 15292385-13 2004 CONCLUSIONS: Patients with P-Akt-positive tumors who received gefitinib had a better response rate, disease control rate, and time to progression than patients with P-Akt-negative tumors, suggesting that gefitinib may be most effective in patients with basal Akt activation. Gefitinib 204-213 AKT serine/threonine kinase 1 Homo sapiens 29-32 15289342-6 2004 Phosphorylation inhibition of downstream effector molecules [mitogen-activated protein kinase (MAPK) and AKT] also was enhanced in tumor cells treated with the combination of cetuximab plus gefitinib or erlotinib. Gefitinib 190-199 AKT serine/threonine kinase 1 Homo sapiens 105-108 15289342-9 2004 Treatment with gefitinib or erlotinib, but not cetuximab, also could further inhibit the activation of downstream effectors of EGFR signaling in cetuximab-resistant cells, including MAPK and AKT. Gefitinib 15-24 AKT serine/threonine kinase 1 Homo sapiens 191-194 15131063-3 2004 EXPERIMENTAL DESIGN: We have determined and quantified how treatment with gefitinib at commonly used, noncytotoxic doses affects neoplastic functions ascribed to EGFRvIII, including downstream signaling by Akt, DNA synthesis, and cellular invasion. Gefitinib 74-83 AKT serine/threonine kinase 1 Homo sapiens 206-209 15269164-5 2004 Ten microm gefitinib inhibited EGFR, p42/44 extracellular signal-regulated kinase (ERK), and Akt/protein kinase B phosphorylation in all three of the cell lines. Gefitinib 11-20 AKT serine/threonine kinase 1 Homo sapiens 93-96 15269164-13 2004 Although gefitinib can inhibit phosphorylation of EGFR, ERK, and Akt, and inhibit growth of bladder cancer cells in vitro, it does not necessarily inhibit growth of bladder cancer cells in vivo. Gefitinib 9-18 AKT serine/threonine kinase 1 Homo sapiens 65-68 15131063-8 2004 This may be due in part to phosphorylation of Akt, which is inhibited in EGFR-expressing cells after treatment with gefitinib, but is unaffected in cells expressing EGFRvIII. Gefitinib 116-125 AKT serine/threonine kinase 1 Homo sapiens 46-49 15078990-0 2004 Sensitivity to gefitinib (Iressa, ZD1839) in non-small cell lung cancer cell lines correlates with dependence on the epidermal growth factor (EGF) receptor/extracellular signal-regulated kinase 1/2 and EGF receptor/Akt pathway for proliferation. Gefitinib 15-24 AKT serine/threonine kinase 1 Homo sapiens 215-218 15078990-6 2004 Phosphorylation of EGFR, protein kinase B/AKT (Akt), and extracellular signal-regulated kinase (ERK) 1/2 was inhibited by much lower concentration of gefitinib in PC9 cells than in the other eight cell lines under exponential growing conditions. Gefitinib 150-159 AKT serine/threonine kinase 1 Homo sapiens 47-50 15078990-8 2004 The present study is the first to demonstrate that sensitivity to growth inhibition by gefitinib in NSCLC cell lines under basal growth condition is associated with dependence on Akt and ERK1/2 activation in response to EGFR signaling for survival and proliferation and also that drug sensitivity may be related to the extent of EGF-induced down-regulation of cell surface EGFR. Gefitinib 87-96 AKT serine/threonine kinase 1 Homo sapiens 179-182 34766965-16 2021 These data are self-sufficient to suggest that NP-dual-3 re-sensitizes the drug-resistant A549/GR cells to gefitinib, possibly by retrieving MET phenomena via modulation of STAT3/mir-21/Akt/PTEN/HIF1-alpha axis. Gefitinib 107-116 AKT serine/threonine kinase 1 Homo sapiens 186-189 14633703-4 2003 Inhibition of ErbB2 by either the HSP (heat shock protein) 90 inhibitor geldanamycin or the ErbB inhibitor ZD1839 in SKBR3 cells, a human breast cancer cell line overexpressing ErbB2 protein, induces a rapid and dramatic decrease in AKT activity. Gefitinib 107-113 AKT serine/threonine kinase 1 Homo sapiens 233-236 14555504-2 2003 We reported previously that both EGFR- and Her2-overexpressing tumors are sensitive to the new EGFR-selective TK inhibitor gefitinib (ZD1839, "Iressa"), and sensitivity to this agent correlated with its ability to down-regulate Akt. Gefitinib 123-132 AKT serine/threonine kinase 1 Homo sapiens 228-231 33772142-0 2022 PPARalpha agonist fenofibrate relieves acquired resistance to gefitinib in non-small cell lung cancer by promoting apoptosis via PPARalpha/AMPK/AKT/FoxO1 pathway. Gefitinib 62-71 AKT serine/threonine kinase 1 Homo sapiens 144-147 34693451-4 2021 Gefitinib inhibits cell viability, tumor growth, cell migration, and invasion and promotes cell apoptosis and G1 cycle arrest in OS at a relatively high concentration via suppressing the PI3K/Akt and ERK pathways. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 192-195 34693451-7 2021 Western blot analysis demonstrates that stattic treatment in gefitinib-treated OS abrogates the IL-6-induced STAT3 activation and subsequently further restrains the activities of EGFR, Akt, and ERK pathways in tumor cells. Gefitinib 61-70 AKT serine/threonine kinase 1 Homo sapiens 185-188 14760103-10 2004 ZD1839 promoted paclitaxel-induced Bcl-2 down-regulation resulting in promoting apoptosis by blocking paclitaxel-induced activation of the EGFR-extracellular signal-regulated kinase antiapoptotic pathway independent of Akt activity in SKRC-49. Gefitinib 0-6 AKT serine/threonine kinase 1 Homo sapiens 219-222 14633703-0 2003 The heat shock protein 90 inhibitor geldanamycin and the ErbB inhibitor ZD1839 promote rapid PP1 phosphatase-dependent inactivation of AKT in ErbB2 overexpressing breast cancer cells. Gefitinib 72-78 AKT serine/threonine kinase 1 Homo sapiens 135-138 34646330-11 2021 QKL injection and TRQ injection increased the sensitivity of gefitinib by inhibiting the phosphorylation of AKT or ERK in H1975 and PC-9-PIK3CA-M cells. Gefitinib 61-70 AKT serine/threonine kinase 1 Homo sapiens 108-111 34581421-13 2021 Moreover, these stimulatory effects of RHBDD1 overexpression on RCC progression and the EGFR/AKT signaling pathway were partly reversed by gefitinib, an EGFR inhibitor. Gefitinib 139-148 AKT serine/threonine kinase 1 Homo sapiens 93-96 34358366-9 2021 CONCLUSION: These data suggests that Gefitinib and Erlotinib prevent activation of downstream signalling proteins MAPK (Thr202/Tyr204) and Akt (Ser473) thereby blocking phenotypic change and cell migration. Gefitinib 37-46 AKT serine/threonine kinase 1 Homo sapiens 139-142 34543169-0 2021 Yang-Yin-Jie-Du decoction overcomes gefitinib resistance in non-small cell lung cancer via down-regulation of the PI3K/Akt signalling pathway. Gefitinib 36-45 AKT serine/threonine kinase 1 Homo sapiens 119-122 34389432-6 2021 Importantly, this novel isoform competes with ASK1 for binding to Akt1, therefore antagonizing Akt1-induced ASK1 phosphorylation and inactivation, leading to the activation of ASK1-induced apoptosis and alleviating gefitinib resistance. Gefitinib 215-224 AKT serine/threonine kinase 1 Homo sapiens 66-70 34389432-6 2021 Importantly, this novel isoform competes with ASK1 for binding to Akt1, therefore antagonizing Akt1-induced ASK1 phosphorylation and inactivation, leading to the activation of ASK1-induced apoptosis and alleviating gefitinib resistance. Gefitinib 215-224 AKT serine/threonine kinase 1 Homo sapiens 95-99 35399731-7 2022 In vivo and in vitro gene functional studies showed that LPCAT1 contributed to the pathogenesis of gefitinib resistance in LUAD, where an LPCAT1-EGFR positive feedback loop formed and then regulated its downstream signaling molecules of the EGFR/PI3K/AKT signaling pathway. Gefitinib 99-108 AKT serine/threonine kinase 1 Homo sapiens 251-254 34510760-6 2021 The gefitinib + anlotinib treatment exerted a synergistic antitumor effect by downregulating the activation of VEGFR2 and downstream effectors, Akt and ERK. Gefitinib 4-13 AKT serine/threonine kinase 1 Homo sapiens 144-147 34681198-3 2021 In addition, it was confirmed by means of isobologram analysis of combinational treatment with gefitinib that they have a synergistic effect, especially compounds 2b and 2f, which inhibit Akt T308 phosphorylation. Gefitinib 95-104 AKT serine/threonine kinase 1 Homo sapiens 188-191 34267282-3 2021 Using spectrometry-based proteomics, we identified increased fibroblast growth factor receptor 1 (FGFR1) expression and Akt activation across erlotinib, gefitinib, and osimertinib EGFR-TKI-resistant cell line models. Gefitinib 153-162 AKT serine/threonine kinase 1 Homo sapiens 120-123 34335947-6 2021 Trop2 was confirmed to induce gefitinib resistance in NSCLC, and Trop2 binding IGF2R promoted the IGF2-IGF1R-Akt axis to enhance gefitinib resistance and remodeling the TME in NSCLC. Gefitinib 129-138 AKT serine/threonine kinase 1 Homo sapiens 109-112 33980216-12 2021 A PI3K/AKT agonist reversed PCAT-1 knockdown-mediated enhancement of gefitinib sensitivity in H1299/GR cells CONCLUSION: PCAT-1 knockdown improves sensitivity to gefitinib by inhibition of AKT and GSK3 phosphorylation in NSCLC. Gefitinib 69-78 AKT serine/threonine kinase 1 Homo sapiens 7-10 35301287-0 2022 Claudin1 decrease induced by 1,25-dihydroxy-vitamin D3 potentiates gefitinib resistance therapy through inhibiting AKT activation-mediated cancer stem-like properties in NSCLC cells. Gefitinib 67-76 AKT serine/threonine kinase 1 Homo sapiens 115-118 35301287-8 2022 Collectively, inhibition of claudin1-mediated cancer stem-like properties by 1,25(OH)2D3 may decrease gefitinib resistance through the AKT pathway, which may be a promising therapeutic strategy for inhibiting gefitinib resistance in EGFR-mutant lung adenocarcinoma. Gefitinib 102-111 AKT serine/threonine kinase 1 Homo sapiens 135-138 35301287-8 2022 Collectively, inhibition of claudin1-mediated cancer stem-like properties by 1,25(OH)2D3 may decrease gefitinib resistance through the AKT pathway, which may be a promising therapeutic strategy for inhibiting gefitinib resistance in EGFR-mutant lung adenocarcinoma. Gefitinib 209-218 AKT serine/threonine kinase 1 Homo sapiens 135-138 33868471-6 2021 The PI3K/Akt signaling pathway was also association with the effects of CNTN1 on EMT progression and gefitinib resistance in the A549 cells. Gefitinib 101-110 AKT serine/threonine kinase 1 Homo sapiens 9-12 33980216-12 2021 A PI3K/AKT agonist reversed PCAT-1 knockdown-mediated enhancement of gefitinib sensitivity in H1299/GR cells CONCLUSION: PCAT-1 knockdown improves sensitivity to gefitinib by inhibition of AKT and GSK3 phosphorylation in NSCLC. Gefitinib 69-78 AKT serine/threonine kinase 1 Homo sapiens 189-192 33980216-12 2021 A PI3K/AKT agonist reversed PCAT-1 knockdown-mediated enhancement of gefitinib sensitivity in H1299/GR cells CONCLUSION: PCAT-1 knockdown improves sensitivity to gefitinib by inhibition of AKT and GSK3 phosphorylation in NSCLC. Gefitinib 162-171 AKT serine/threonine kinase 1 Homo sapiens 7-10 33529999-9 2021 Surprisingly, while gefitinib-resistant cells were independent of EGFR for survival, they nonetheless displayed activation of downstream ERK and AKT signalling. Gefitinib 20-29 AKT serine/threonine kinase 1 Homo sapiens 145-148 33491264-0 2021 RNA methyltransferase METTL3 induces intrinsic resistance to gefitinib by combining with MET to regulate PI3K/AKT pathway in lung adenocarcinoma. Gefitinib 61-70 AKT serine/threonine kinase 1 Homo sapiens 110-113 32894437-0 2021 Y-box binding protein 1 (YB-1) promotes gefitinib resistance in lung adenocarcinoma cells by activating AKT signaling and epithelial-mesenchymal transition through targeting major vault protein (MVP). Gefitinib 40-49 AKT serine/threonine kinase 1 Homo sapiens 104-107 32894437-10 2021 YB-1 augmented gefitinib resistance by activating the AKT pathway and promoting EMT. Gefitinib 15-24 AKT serine/threonine kinase 1 Homo sapiens 54-57 33491264-6 2021 Mechanistic studies have shown that METTL3 combines with MET and causes the PI3K/AKT signalling pathway to be manipulated, which affects the sensitivity of lung cancer cells to gefitinib. Gefitinib 177-186 AKT serine/threonine kinase 1 Homo sapiens 81-84 32963612-11 2020 Gefitinib resistance induced by hyperinsulinemia may have been mediated via the phosphoinositide 3-kinase (PI3K)/AKT pathway rather than the mitogen-activated protein kinase extracellular signal regulated kinase (MAPK/ERK) pathway. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 113-116 32956565-0 2020 M2 macrophages reduce the effect of gefitinib by activating AKT/mTOR in gefitinib-resistant cell lines HCC827/GR. Gefitinib 36-45 AKT serine/threonine kinase 1 Homo sapiens 60-63 32956565-0 2020 M2 macrophages reduce the effect of gefitinib by activating AKT/mTOR in gefitinib-resistant cell lines HCC827/GR. Gefitinib 72-81 AKT serine/threonine kinase 1 Homo sapiens 60-63 32956565-10 2020 M2 macrophages reduced the antitumor effect of gefitinib treatment by activating AKT/mTOR. Gefitinib 47-56 AKT serine/threonine kinase 1 Homo sapiens 81-84 32963612-12 2020 AKT serine/threonine kinase 1 knockdown by siRNA rescued the gefitinib resistance that was induced by hyperinsulinemia. Gefitinib 61-70 AKT serine/threonine kinase 1 Homo sapiens 0-29 32820249-7 2020 Therefore, we conclude that miR-450a-5p synergizes with gefitinib to inhibit the glioma tumorigenesis through inducing autophagy by regulating the EGFR-induced PI3K/AKT/mTOR signaling pathway, thereby enhancing the drug sensitivity of gefitinib. Gefitinib 56-65 AKT serine/threonine kinase 1 Homo sapiens 165-168 32895203-9 2020 Gefitinib significantly lowered intracellular lactic acid level of the cells (P < 0.05) and down-regulated the expressions of PKM2 and HK2 proteins (P < 0.05) and PI3K-Akt-mTOR signaling pathway-associated proteins (P < 0.05). Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 168-171 32489321-2 2020 Our basic study found that FZKA decoction could enhance the inhibition effect of GFTN in lung cancer by inactivating PI3K/Akt pathway. Gefitinib 81-85 AKT serine/threonine kinase 1 Homo sapiens 122-125 32895203-15 2020 Gefitinib induces apoptosis of the cells possibly by affecting glycolysis and PI3K-Akt-mTOR signaling pathway. Gefitinib 0-9 AKT serine/threonine kinase 1 Homo sapiens 83-86 32004572-7 2020 Protein kinase array further suggested that ID1 overexpression maintains Akt activity in gefitinib-treated NSCLC cells, which in turn upregulated FLICE-like inhibitory protein to dissociate the caspase-8-RIP1 complex. Gefitinib 89-98 AKT serine/threonine kinase 1 Homo sapiens 73-76 31310954-0 2019 An effective drug sensitizing agent increases gefitinib treatment by down regulating PI3K/Akt/mTOR pathway and up regulating autophagy in non-small cell lung cancer. Gefitinib 46-55 AKT serine/threonine kinase 1 Homo sapiens 90-93 32552611-0 2020 Combination therapy of gefitinib and miR-30a-5p may overcome acquired drug resistance through regulating the PI3K/AKT pathway in non-small cell lung cancer. Gefitinib 23-32 AKT serine/threonine kinase 1 Homo sapiens 114-117 31310954-7 2019 This could be the results of down regulation of the PI3K/Akt/mTOR pathway and up regulation of autophagy, which were identified as the potential primary targets of CKI to increase gefitinib treatment effect. Gefitinib 180-189 AKT serine/threonine kinase 1 Homo sapiens 57-60 31132355-9 2019 Further study revealed that the inhibitors of AKT, MEK/ERK, and p38 increased the antiproliferative and proapoptotic effects of the combined treatment of thalidomide and gefitinib. Gefitinib 170-179 AKT serine/threonine kinase 1 Homo sapiens 46-49