PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 33776476-0 2021 Erratum: Oridonin Sensitizes Hepatocellular Carcinoma to the Anticancer Effect of Sorafenib by Targeting the Akt Pathway [Corrigendum]. Sorafenib 82-91 AKT serine/threonine kinase 1 Homo sapiens 109-112 34916846-0 2021 Hypoxia-Induced Aquaporin-3 Changes Hepatocellular Carcinoma Cell Sensitivity to Sorafenib by Activating the PI3K/Akt Signaling Pathway (Retraction). Sorafenib 81-90 AKT serine/threonine kinase 1 Homo sapiens 114-117 34765572-11 2021 Discussion: The results demonstrated that CYP2C8 enhances the anticancer activity of sorafenib in vitro assays and in tumor xenograft model, with Ki-67 down-regulation and PI3K/Akt/p27Kip1 axis inhibition. Sorafenib 85-94 AKT serine/threonine kinase 1 Homo sapiens 177-180 34950583-0 2021 SENP2 Reduces Hepatocellular Carcinoma Stemness and Improves Sorafenib Sensitivity Through Inactivating the AKT/GSK3beta/CTNNB1 Pathway. Sorafenib 61-70 AKT serine/threonine kinase 1 Homo sapiens 108-111 34950583-7 2021 The following compensation experiment revealed that activating AKT or overexpressing CTNNB1 promoted CD133+ cell proportion and sphere formation ability but suppressed sorafenib sensitivity in Huh7 and Hep3B cells. Sorafenib 168-177 AKT serine/threonine kinase 1 Homo sapiens 63-66 34950583-8 2021 Moreover, activating AKT or overexpressing CTNNB1 attenuated the effect of SENP2 overexpression on stemness and sorafenib sensitivity in Huh7 and Hep3B cells. Sorafenib 112-121 AKT serine/threonine kinase 1 Homo sapiens 21-24 34950583-9 2021 Conclusion: SENP2 suppresses HCC stemness and increases sorafenib sensitivity through inactivating the AKT/GSK3beta/CTNNB1 signaling pathway. Sorafenib 56-65 AKT serine/threonine kinase 1 Homo sapiens 103-106 34852817-0 2021 Correction to: LncRNA SNHG1 contributes to sorafenib resistance by activating the Akt pathway and is positively regulated by miR-21 in hepatocellular carcinoma cells. Sorafenib 43-52 AKT serine/threonine kinase 1 Homo sapiens 82-85 34768109-5 2021 Importantly, activation of PI3K/AKT/NRF2 axis was essential for sorafenib to induce ABCC5 expression. Sorafenib 64-73 AKT serine/threonine kinase 1 Homo sapiens 32-35 34765572-12 2021 In conclusion, these findings hinted that CYP2C8 restricted malignant phenotype and sorafenib resistance in HCC via PI3K/Akt/p27kip1 axis. Sorafenib 84-93 AKT serine/threonine kinase 1 Homo sapiens 121-124 34366628-0 2021 Y-box binding protein 1 augments sorafenib resistance via the PI3K/Akt signaling pathway in hepatocellular carcinoma. Sorafenib 33-42 AKT serine/threonine kinase 1 Homo sapiens 67-70 34725436-7 2021 Akt suppression following sorafenib treatment resulted in an increase of the H3K27me3 levels through a decrease in EZH2 phosphorylation at serine 21. Sorafenib 26-35 AKT serine/threonine kinase 1 Homo sapiens 0-3 34632072-5 2021 Also, perversely upregulated PI3K/AKT signaling Huh7 cells are highly resistant to treatment with chemotherapy drugs (docetaxel and sorafenib) and acquired apoptosis resistance through downregulation of tumor suppressor protein PTEN (phosphatase and tensin homolog deleted on chromosome ten). Sorafenib 132-141 AKT serine/threonine kinase 1 Homo sapiens 34-37 34366628-13 2021 Furthermore, KEGG pathway enrichment analysis of DGE-seq demonstrated that the phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was essential for the sorafenib resistance induced by YB-1. Sorafenib 175-184 AKT serine/threonine kinase 1 Homo sapiens 130-133 34366628-15 2021 Finally, YB-1 suppressed the inactivation of the PI3K/Akt signaling pathway induced by sorafenib, and the blockade of the PI3K/Akt signaling pathway by LY294002 mitigated YB-1-induced sorafenib resistance. Sorafenib 87-96 AKT serine/threonine kinase 1 Homo sapiens 54-57 34076140-0 2021 MicroRNA-92b augments sorafenib resistance in hepatocellular carcinoma via targeting PTEN to activate PI3K/AKT/mTOR signaling. Sorafenib 22-31 AKT serine/threonine kinase 1 Homo sapiens 107-110 34445279-8 2021 Herein, we showed that NPC2 downregulation and free cholesterol accumulation weakened sorafenib"s efficacy through enhancing MAPK/AKT signaling in HCC cells. Sorafenib 86-95 AKT serine/threonine kinase 1 Homo sapiens 130-133 34377232-0 2021 Phenformin synergistically sensitizes liver cancer cells to sorafenib by downregulating CRAF/ERK and PI3K/AKT/mTOR pathways. Sorafenib 60-69 AKT serine/threonine kinase 1 Homo sapiens 106-109 34377232-7 2021 Phenformin further bolstered the ability of sorafenib to inhibit the CRAF/ERK and PI3K/AKT/mTOR pathways. Sorafenib 44-53 AKT serine/threonine kinase 1 Homo sapiens 87-90 34377232-9 2021 Sorafenib and phenformin can synergistically suppress CRAF/ERK and PI3K/AKT/mTOR pathway activation in HCC cells, and may thus represent a promising approach to treating this deadly cancer. Sorafenib 0-9 AKT serine/threonine kinase 1 Homo sapiens 72-75 34076140-9 2021 Furthermore, we confirmed by western blotting and immunofluorescence that miR-92b can mediate sorafenib resistance by activating the PI3K/AKT/mTOR pathway in HCC cells by directly targeting PTEN. Sorafenib 94-103 AKT serine/threonine kinase 1 Homo sapiens 138-141 35359392-0 2022 Knockdown of AKR1C3 Promoted Sorafenib Sensitivity Through Inhibiting the Phosphorylation of AKT in Hepatocellular Carcinoma. Sorafenib 29-38 AKT serine/threonine kinase 1 Homo sapiens 93-96 35244188-11 2022 Co-treatment with harmine and either regorafenib or sorafenib also promoted cell death via the STAT3/HIF-1alpha/AKT signaling pathway under hypoxia using PI staining and western blotting. Sorafenib 52-61 AKT serine/threonine kinase 1 Homo sapiens 112-115 35359392-12 2022 Conclusion: AKR1C3 can induce sorafenib resistance through promoting the phosphorylation of AKT in HCC. Sorafenib 30-39 AKT serine/threonine kinase 1 Homo sapiens 92-95 35111229-11 2022 Taken together, the present study revealed a novel molecular mechanism by which tangeretin may inhibit the proliferation of CRPC cells, by affecting the Cx26/AKT/AR pathway, to synergistically increase the sensitivity of CRPC cells to sorafenib and cisplatin. Sorafenib 235-244 AKT serine/threonine kinase 1 Homo sapiens 158-161 33735117-0 2021 Enhanced anticancer activity by the combination of vinpocetine and sorafenib via PI3K/AKT/GSK-3beta signaling axis in hepatocellular carcinoma cells. Sorafenib 67-76 AKT serine/threonine kinase 1 Homo sapiens 86-89 33667419-7 2021 Overexpression simulations identified Akt, IGF1, PDK1, and PI3K among the negative functional regulators of sorafenib-induced cardiomyocyte apoptosis. Sorafenib 108-117 AKT serine/threonine kinase 1 Homo sapiens 38-41 33951569-13 2021 The present study also provides mechanistic evidence that PRIS modulated the Akt/FoxO1/p27kip1 signaling pathway, which is required for mitochondrial-mediated intrinsic apoptosis, activation of ER stress, and stimulation of caspase-4 induced by PRIS, and, consequently resulting in suppressed cell viability, migration and angiogenesis co-treated with SORA in CRHCs. Sorafenib 352-356 AKT serine/threonine kinase 1 Homo sapiens 77-80 34030133-0 2021 NUPR1 is a novel potential biomarker and confers resistance to sorafenib in clear cell renal cell carcinoma by increasing stemness and targeting the PTEN/AKT/mTOR pathway. Sorafenib 63-72 AKT serine/threonine kinase 1 Homo sapiens 154-157 34026624-7 2021 Of interest, PD only promoted the anti-cancer effects of sorafenib in Akt-positive and PTEN-negative prostate cancer cells. Sorafenib 57-66 AKT serine/threonine kinase 1 Homo sapiens 70-73 33987439-0 2021 BEZ235 Increases the Sensitivity of Hepatocellular Carcinoma to Sorafenib by Inhibiting PI3K/AKT/mTOR and Inducing Autophagy. Sorafenib 64-73 AKT serine/threonine kinase 1 Homo sapiens 93-96 33987439-9 2021 SFB + BEZ inhibited the activation of the PI3K/AKT/mTOR pathway caused by sorafenib. Sorafenib 74-83 AKT serine/threonine kinase 1 Homo sapiens 47-50 33987439-13 2021 We concluded that BEZ235 enhanced the sensitivity of sorafenib through suppressing the PI3K/AKT/mTOR pathway and inducing autophagy. Sorafenib 53-62 AKT serine/threonine kinase 1 Homo sapiens 92-95 33517269-5 2021 RESULTS: Sorafenib increased uPA secretion, which was abrogated by an Akt inhibitor. Sorafenib 9-18 AKT serine/threonine kinase 1 Homo sapiens 70-73 33051131-0 2020 Torin2 overcomes sorafenib resistance via suppressing mTORC2-AKT-BAD pathway in hepatocellular carcinoma cells. Sorafenib 17-26 AKT serine/threonine kinase 1 Homo sapiens 61-64 32510618-11 2021 Furthermore, we also found the PI3K/AKT pathway was involved in sorafenib-induced resistance and ITE could restore sensitivity by suppressing the PI3K/AKT pathway. Sorafenib 64-73 AKT serine/threonine kinase 1 Homo sapiens 36-39 32510618-11 2021 Furthermore, we also found the PI3K/AKT pathway was involved in sorafenib-induced resistance and ITE could restore sensitivity by suppressing the PI3K/AKT pathway. Sorafenib 64-73 AKT serine/threonine kinase 1 Homo sapiens 151-154 33379356-5 2020 Phosphoinositide-3-kinase (PI3K) and protein kinase B (AKT) were activated by sorafenib, which, in turn, increased the phosphorylation level of YB-1. Sorafenib 78-87 AKT serine/threonine kinase 1 Homo sapiens 55-58 33379356-10 2020 Our collective findings suggest that sorafenib promotes YB-1 phosphorylation through effect from the EGFR/PI3K/AKT pathway, leading to significant enhancement of hepatocellular carcinoma (HCC) cell metastasis. Sorafenib 37-46 AKT serine/threonine kinase 1 Homo sapiens 111-114 33051131-7 2020 RESULTS: Sorafenib treatment inversely inhibited AKT in parental but activated AKT in sorafenib-resistant Huh7 and Hep3B HCC cells, which underscores the significance of AKT activation. Sorafenib 9-18 AKT serine/threonine kinase 1 Homo sapiens 49-52 33051131-7 2020 RESULTS: Sorafenib treatment inversely inhibited AKT in parental but activated AKT in sorafenib-resistant Huh7 and Hep3B HCC cells, which underscores the significance of AKT activation. Sorafenib 9-18 AKT serine/threonine kinase 1 Homo sapiens 79-82 33051131-7 2020 RESULTS: Sorafenib treatment inversely inhibited AKT in parental but activated AKT in sorafenib-resistant Huh7 and Hep3B HCC cells, which underscores the significance of AKT activation. Sorafenib 9-18 AKT serine/threonine kinase 1 Homo sapiens 79-82 33051131-9 2020 Torin2 successfully suppressed the sorafenib-activated mTORC2-AKT axis, leading to the dephosphorylation of Ser136 in BAD protein, and increased the expression of total BAD, which contributed to the apoptosis in sorafenib-resistant HCC cells. Sorafenib 35-44 AKT serine/threonine kinase 1 Homo sapiens 62-65 33051131-10 2020 CONCLUSIONS: In this study, Torin2 and sorafenib showed synergistic cytostatic capacity in sorafenib-resistant HCC cells, via the suppression of mTORC2-AKT-BAD pathway. Sorafenib 39-48 AKT serine/threonine kinase 1 Homo sapiens 152-155 33051131-10 2020 CONCLUSIONS: In this study, Torin2 and sorafenib showed synergistic cytostatic capacity in sorafenib-resistant HCC cells, via the suppression of mTORC2-AKT-BAD pathway. Sorafenib 91-100 AKT serine/threonine kinase 1 Homo sapiens 152-155 33112540-7 2020 qPCR and western blot revealed that a combination of Sorafenib (10 mumol/L) and cisplatinum (10 mg/L) reduced the transcription and protein expression of autophagy-related AKT and mTOR but increased that of LC3 (P <0.05). Sorafenib 53-62 AKT serine/threonine kinase 1 Homo sapiens 172-175 33097691-11 2020 We also show the vital role of CLCF1 in promoting glycolysis by activating PI3K/AKT signaling and its downstream genes, thus participating in glycolysis in sorafenib-resistant HCC cells. Sorafenib 156-165 AKT serine/threonine kinase 1 Homo sapiens 80-83 33112540-8 2020 CONCLUSION: Combining Sorafenib and cisplatinum can effectively induce cell autophagy and reduce cellular proliferation via the PI3K/AKT/mTOR signal pathway.
. Sorafenib 22-31 AKT serine/threonine kinase 1 Homo sapiens 133-136 32203105-8 2020 The attenuation of sorafenib resistance may be achieved prior to its development through the modulation of EphA2 and the subsequent inhibition of Akt activity. Sorafenib 19-28 AKT serine/threonine kinase 1 Homo sapiens 146-149 33015852-0 2021 Valproic acid reverses Sorafenib resistance through inhibiting activated Notch/Akt signaling pathway in HCC. Sorafenib 23-32 AKT serine/threonine kinase 1 Homo sapiens 79-82 33015852-6 2021 Thorough comparisons of the molecular changes between parental HepG2 and sorafenib-resistant HepG2-SR cells indicated that the Notch signaling pathway and PI3K/Akt signaling pathway were associated with sorafenib resistance mechanisms. Sorafenib 73-82 AKT serine/threonine kinase 1 Homo sapiens 160-163 33015852-6 2021 Thorough comparisons of the molecular changes between parental HepG2 and sorafenib-resistant HepG2-SR cells indicated that the Notch signaling pathway and PI3K/Akt signaling pathway were associated with sorafenib resistance mechanisms. Sorafenib 203-212 AKT serine/threonine kinase 1 Homo sapiens 160-163 33015852-7 2021 Notch1 and Akt were up-regulated in sorafenib-resistant cells. Sorafenib 36-45 AKT serine/threonine kinase 1 Homo sapiens 11-14 33015852-8 2021 However, we surprisingly found that VPA combined with sorafenib could enhance the sensitivity of drug-resistant cells and reverse the increased levels of Notch1 and Akt in sorafenib-resistant HCC cells. Sorafenib 54-63 AKT serine/threonine kinase 1 Homo sapiens 165-168 33015852-8 2021 However, we surprisingly found that VPA combined with sorafenib could enhance the sensitivity of drug-resistant cells and reverse the increased levels of Notch1 and Akt in sorafenib-resistant HCC cells. Sorafenib 172-181 AKT serine/threonine kinase 1 Homo sapiens 165-168 33015852-11 2021 Collectively, our results indicated that Notch1 and Akt might play vital roles in sorafenib resistance in HCC cells and VPA might overcome the drug resistance to enhance the sensitivity of HCC cells to sorafenib through suppressing Notch/Akt signaling pathway. Sorafenib 82-91 AKT serine/threonine kinase 1 Homo sapiens 52-55 32970612-8 2020 The synergistic antitumor effects of sorafenib and GHR knockdown combination may be attributed to inhibition of PI3K/AKT/ERK1/2 signaling pathway. Sorafenib 37-46 AKT serine/threonine kinase 1 Homo sapiens 117-120 33163195-13 2020 PD-L1 promoted the EMT of sorafenib-resistant HCC cells via the PI3K/Akt pathway by activating SREBP-1 expression in HepG2 SR and Huh7 SR cells. Sorafenib 26-35 AKT serine/threonine kinase 1 Homo sapiens 69-72 32982405-0 2020 Oridonin Sensitizes Hepatocellular Carcinoma to the Anticancer Effect of Sorafenib by Targeting the Akt Pathway. Sorafenib 73-82 AKT serine/threonine kinase 1 Homo sapiens 100-103 32504550-3 2020 Pancreatic tumors previously exposed to [sorafenib + vorinostat] evolved to activate the receptors ERBB1, ERBB2, ERBB3, c-MET and the intracellular kinase AKT. Sorafenib 41-50 AKT serine/threonine kinase 1 Homo sapiens 155-158 32606928-0 2020 Hypoxia-Induced Aquaporin-3 Changes Hepatocellular Carcinoma Cell Sensitivity to Sorafenib by Activating the PI3K/Akt Signaling Pathway. Sorafenib 81-90 AKT serine/threonine kinase 1 Homo sapiens 114-117 32461380-0 2020 LncRNA NEAT1 modulates sorafenib resistance in hepatocellular carcinoma through regulating the miR-149-5p/AKT1 axis. Sorafenib 23-32 AKT serine/threonine kinase 1 Homo sapiens 106-110 32391926-6 2022 Sorafenib reduced phosphorylation of AKT and ERK, suggesting that sorafenib induces pigmentation through inhibition of the AKT and ERK pathways. Sorafenib 0-9 AKT serine/threonine kinase 1 Homo sapiens 37-40 32391926-6 2022 Sorafenib reduced phosphorylation of AKT and ERK, suggesting that sorafenib induces pigmentation through inhibition of the AKT and ERK pathways. Sorafenib 0-9 AKT serine/threonine kinase 1 Homo sapiens 123-126 32391926-6 2022 Sorafenib reduced phosphorylation of AKT and ERK, suggesting that sorafenib induces pigmentation through inhibition of the AKT and ERK pathways. Sorafenib 66-75 AKT serine/threonine kinase 1 Homo sapiens 37-40 32391926-6 2022 Sorafenib reduced phosphorylation of AKT and ERK, suggesting that sorafenib induces pigmentation through inhibition of the AKT and ERK pathways. Sorafenib 66-75 AKT serine/threonine kinase 1 Homo sapiens 123-126 31385002-11 2019 Sorafenib and CMG002 as single agents differentially inhibited or activated key enzymes in the Ras/Raf/MAPK and PI3K/AKT/mTOR pathways. Sorafenib 0-9 AKT serine/threonine kinase 1 Homo sapiens 117-120 30663411-0 2019 Activation of MET promotes resistance to sorafenib in hepatocellular carcinoma cells via the AKT/ERK1/2-EGR1 pathway. Sorafenib 41-50 AKT serine/threonine kinase 1 Homo sapiens 93-96 30663411-4 2019 In this study, we found that addition of HGF to sorafenib-treated HCC cells activated MET and re-stimulated the downstream AKT and ERK1/2 pathways. Sorafenib 48-57 AKT serine/threonine kinase 1 Homo sapiens 123-126 31439713-1 2019 Activation of PI3K/Akt/mTOR pathway is an important signaling mechanism involved in the development and the progression of liver cancer stem cell (LCSC) population during acquired Sorafenib resistance in advanced Hepatocellular carcinoma (HCC). Sorafenib 180-189 AKT serine/threonine kinase 1 Homo sapiens 19-22 31385002-16 2019 CONCLUSIONS: The combination of CMG002 and sorafenib significantly inhibited HCC cell proliferation and tumorigenesis by inhibiting the Ras/Raf/MAPK and PI3K/AKT/mTOR pathways. Sorafenib 43-52 AKT serine/threonine kinase 1 Homo sapiens 158-161 30456603-0 2019 The novel PI3K inhibitor S1 synergizes with sorafenib in non-small cell lung cancer cells involving the Akt-S6 signaling. Sorafenib 44-53 AKT serine/threonine kinase 1 Homo sapiens 104-107 30456603-8 2019 The combination of S1 and sorafenib exerts potentiated anti-tumor effects, in which the underlying mechanisms may involve their differential modulation of the phosphorylation of Akt and S6 in the PI3K/Akt/mTOR cascades and ERK phosphorylation in the Raf/MEK/ERK pathways. Sorafenib 26-35 AKT serine/threonine kinase 1 Homo sapiens 178-181 30456603-8 2019 The combination of S1 and sorafenib exerts potentiated anti-tumor effects, in which the underlying mechanisms may involve their differential modulation of the phosphorylation of Akt and S6 in the PI3K/Akt/mTOR cascades and ERK phosphorylation in the Raf/MEK/ERK pathways. Sorafenib 26-35 AKT serine/threonine kinase 1 Homo sapiens 201-204 31387809-7 2019 Furthermore, sorafenib significantly inhibited cell proliferation, IL-6 level and activation of p-PI3K/AKT while promoted the cell apoptosis rate and Caspase3 level compared as the control group, which were further promoted by administration of si IL-6. Sorafenib 13-22 AKT serine/threonine kinase 1 Homo sapiens 103-106 31233204-0 2019 Synergistic antitumor effect of BRMS1 and sorafenib via inhibition of the PI3K/AKT/mTOR/ERK signaling pathway. Sorafenib 42-51 AKT serine/threonine kinase 1 Homo sapiens 79-82 31233204-7 2019 In addition, expression of inflammatory response-related genes was increased, while secretion of angiogenesis-related molecules was decreased, and apoptosis was also activated after sorafenib treatment using qPCR method, and it was further demonstrated that this effect was mediated by inhibition of the PI3K/AKT/mTOR/ERK signaling pathway using western blot analysis. Sorafenib 182-191 AKT serine/threonine kinase 1 Homo sapiens 309-312 31233204-8 2019 In conclusion, overexpression of BRMS1 potentiated the effect of sorafenib via PI3K/AKT/mTOR/ERK signaling, while knockdown of BRMS1 expression attenuated this effect. Sorafenib 65-74 AKT serine/threonine kinase 1 Homo sapiens 84-87 31698564-12 2019 Moreover, our study showed Akt signaling was aberrantly activated and inhibition of Akt signaling enhanced anti-tumor capacity of sorafenib in sorafenib-resistant HCC cells. Sorafenib 130-139 AKT serine/threonine kinase 1 Homo sapiens 84-87 31233189-0 2019 Activation of AKT/AP1/FoxM1 signaling confers sorafenib resistance to liver cancer cells. Sorafenib 46-55 AKT serine/threonine kinase 1 Homo sapiens 14-17 31233189-10 2019 Inhibition of AKT using BEZ-235 markedly suppressed the upregulation of c-jun and FoxM1, and increased the sensitivity of drug-resistant cells to sorafenib in vitro and in vivo. Sorafenib 146-155 AKT serine/threonine kinase 1 Homo sapiens 14-17 31233189-11 2019 The data indicated that the activation of the AKT/AP1/FoxM1 signaling axis is an important determinant of sorafenib tolerance. Sorafenib 106-115 AKT serine/threonine kinase 1 Homo sapiens 46-49 31698564-12 2019 Moreover, our study showed Akt signaling was aberrantly activated and inhibition of Akt signaling enhanced anti-tumor capacity of sorafenib in sorafenib-resistant HCC cells. Sorafenib 143-152 AKT serine/threonine kinase 1 Homo sapiens 84-87 31053148-0 2019 LncRNA SNHG1 contributes to sorafenib resistance by activating the Akt pathway and is positively regulated by miR-21 in hepatocellular carcinoma cells. Sorafenib 28-37 AKT serine/threonine kinase 1 Homo sapiens 67-70 31417635-13 2019 Finally, we have identified a novel KPNA3-AKT-ERK-TWIST signaling cascade that promotes EMT and mediates sorafenib resistance in HCC. Sorafenib 105-114 AKT serine/threonine kinase 1 Homo sapiens 42-45 31053148-3 2019 The present study aims to explore the involvement of lncRNA SNHG1 (small nucleolar RNA host gene 1) in sorafenib resistance and how SNHG1 is associated with overexpressed microRNA-21 (miR-21) and the activated Akt pathway, which have been demonstrated to mediate this resistance in HCC cells. Sorafenib 103-112 AKT serine/threonine kinase 1 Homo sapiens 210-213 31053148-12 2019 Overexpressed SNHG1 contributes to sorafenib resistance by activating the Akt pathway via regulating SLC3A2. Sorafenib 35-44 AKT serine/threonine kinase 1 Homo sapiens 74-77 31053148-13 2019 Depletion of SNHG1 enhanced the efficacy of sorafenib to induce apoptosis and autophagy of SR-HCC cells by inhibiting the activation of Akt pathway. Sorafenib 44-53 AKT serine/threonine kinase 1 Homo sapiens 136-139 31053148-14 2019 Sorafenib induced translocation of miR-21 to the nucleus, where it promoted the expression of SNHG1, resulting in upregulation of SLC3A2, leading to the activation of Akt pathway. Sorafenib 0-9 AKT serine/threonine kinase 1 Homo sapiens 167-170 31053148-16 2019 CONCLUSIONS: The present study has demonstrated that lncRNA SNHG1 contributes to sorafenib resistance by activating the Akt pathway and its nuclear expression is promoted by miR-21, whose nuclear translocation is induced by sorafenib. Sorafenib 81-90 AKT serine/threonine kinase 1 Homo sapiens 120-123 31053148-16 2019 CONCLUSIONS: The present study has demonstrated that lncRNA SNHG1 contributes to sorafenib resistance by activating the Akt pathway and its nuclear expression is promoted by miR-21, whose nuclear translocation is induced by sorafenib. Sorafenib 224-233 AKT serine/threonine kinase 1 Homo sapiens 120-123 30369518-15 2018 And we found that 786-O RCC cells secrete high IL-6 levels after low dose stimulation with the TKIs sorafenib, sunitinib and pazopanib, inducing activation of AKT-mTOR pathway, NFkappaB, HIF-2alpha and VEGF expression. Sorafenib 100-109 AKT serine/threonine kinase 1 Homo sapiens 159-162 30975543-13 2019 Sorafenib, through AMPK, blocked the GDNF/AKT survival action without altering the RET apoptotic pathway. Sorafenib 0-9 AKT serine/threonine kinase 1 Homo sapiens 42-45 30142009-4 2019 Exposure to [sorafenib + vorinostat] reduced the expression of beta-catenin, ERBB1, BCL-XL and MCL-1, and the phosphorylation of AKT T308, AKT S473, GSK3 S9/21, mTORC1 and mTORC2. Sorafenib 13-22 AKT serine/threonine kinase 1 Homo sapiens 129-132 30142009-4 2019 Exposure to [sorafenib + vorinostat] reduced the expression of beta-catenin, ERBB1, BCL-XL and MCL-1, and the phosphorylation of AKT T308, AKT S473, GSK3 S9/21, mTORC1 and mTORC2. Sorafenib 13-22 AKT serine/threonine kinase 1 Homo sapiens 139-142 30292139-5 2018 Mechanism dissection suggests that the combination of MLN8237 and sorafenib led to significant inhibition of the activation of phospho-Akt (p-Akt) and phospho-p38 mitogen-activated protein kinase (p-p38 MAPK) and their downstream genes including CDK4, cyclinD1, and VEGFA. Sorafenib 66-75 AKT serine/threonine kinase 1 Homo sapiens 135-138 30292139-5 2018 Mechanism dissection suggests that the combination of MLN8237 and sorafenib led to significant inhibition of the activation of phospho-Akt (p-Akt) and phospho-p38 mitogen-activated protein kinase (p-p38 MAPK) and their downstream genes including CDK4, cyclinD1, and VEGFA. Sorafenib 66-75 AKT serine/threonine kinase 1 Homo sapiens 142-145 30292139-6 2018 The activators of p-Akt and p-p38 MAPK signaling partially reversed the synergistic inhibitory effects of sorafenib and MLN8237 on HCC progression. Sorafenib 106-115 AKT serine/threonine kinase 1 Homo sapiens 20-23 30272354-0 2018 Capsaicin and sorafenib combination treatment exerts synergistic anti-hepatocellular carcinoma activity by suppressing EGFR and PI3K/Akt/mTOR signaling. Sorafenib 14-23 AKT serine/threonine kinase 1 Homo sapiens 133-136 30443188-3 2018 In our study, we evaluated effect of quisinostat alone and in combination with sorafenib in HCC cells via inducing G0/G1 phase arrest through PI3K/AKT/p21 pathway and apoptosis by JNK/c-Jun/caspase3 pathway in vitro and in vivo. Sorafenib 79-88 AKT serine/threonine kinase 1 Homo sapiens 147-150 30311444-10 2018 Taken together, our study demonstrates that SESN2 activates AKT and AMPK signaling as a novel mechanism to induce sorafenib primary resistance in HCC. Sorafenib 114-123 AKT serine/threonine kinase 1 Homo sapiens 60-63 30021351-6 2018 Moreover, aberrant expression of miR-19a-3p induced sorafenib resistance by regulating the PTEN/Akt pathway. Sorafenib 52-61 AKT serine/threonine kinase 1 Homo sapiens 96-99 29782854-0 2018 Combined treatment with sorafenib and silibinin synergistically targets both HCC cells and cancer stem cells by enhanced inhibition of the phosphorylation of STAT3/ERK/AKT. Sorafenib 24-33 AKT serine/threonine kinase 1 Homo sapiens 168-171 30154433-9 2018 In acquired sorafenib-resistant cells, ID1 low expression, p16/IL6 axis up-regulation, and AKT phosphorylation activation were observed. Sorafenib 12-21 AKT serine/threonine kinase 1 Homo sapiens 91-94 30154433-10 2018 A reduced cytotoxicity of sorafenib was detected when sorafenib-sensitive cells incubated with conditioned media from the resistant cells, accompanied by the stimulation of AKT phosphorylation. Sorafenib 26-35 AKT serine/threonine kinase 1 Homo sapiens 173-176 30154433-11 2018 The reversal of sorafenib resistance could be achieved through ID1 overexpression, IL6 blocking, and AKT pathway inhibition. Sorafenib 16-25 AKT serine/threonine kinase 1 Homo sapiens 101-104 30048489-0 2018 Autophagic cell death associated to Sorafenib in renal cell carcinoma is mediated through Akt inhibition in an ERK1/2 independent fashion. Sorafenib 36-45 AKT serine/threonine kinase 1 Homo sapiens 90-93 30112114-1 2018 Efficient combinations of sorafenib with targeted inhibitors blocking AKT/mTOR. Sorafenib 26-35 AKT serine/threonine kinase 1 Homo sapiens 70-73 30112114-9 2018 The combination of sorafenib with targeted therapies exhibited synergistic anti-HCC biological activity concomitantly with highly effective inhibition of MAPK and AKT/mTOR signaling. Sorafenib 19-28 AKT serine/threonine kinase 1 Homo sapiens 163-166 30048489-5 2018 Furthermore, we demonstrate that inhibition of Akt mediates cell death associated to Sorafenib without caspase activation, and this is consistent with the induction of autophagy, as indicated by the use of pharmacological and genetic approaches. Sorafenib 85-94 AKT serine/threonine kinase 1 Homo sapiens 47-50 30048489-6 2018 CONCLUSION: The present report demonstrates that Sorafenib exerts its toxic effect through the induction of autophagy in an Akt-dependent fashion without the implication of Mitogen Activated Protein Kinase. Sorafenib 49-58 AKT serine/threonine kinase 1 Homo sapiens 124-127 29928334-0 2018 Inhibition of the PI3K/Akt signaling pathway reverses sorafenib-derived chemo-resistance in hepatocellular carcinoma. Sorafenib 54-63 AKT serine/threonine kinase 1 Homo sapiens 23-26 29538717-0 2018 Sorafenib inhibits proliferation and invasion in desmoid-derived cells by targeting Ras/MEK/ERK and PI3K/Akt/mTOR pathways. Sorafenib 0-9 AKT serine/threonine kinase 1 Homo sapiens 105-108 29538717-4 2018 Sorafenib is a multikinase inhibitor with known antitumor activity in various cancers via suppression of the PI3K/Akt/mTOR pathway. Sorafenib 0-9 AKT serine/threonine kinase 1 Homo sapiens 114-117 29538717-7 2018 Signaling arrays identified multiple potential targets of sorafenib in the Ras/MEK/ERK and PI3K/Akt/mTOR signaling cascades. Sorafenib 58-67 AKT serine/threonine kinase 1 Homo sapiens 96-99 29538717-8 2018 Immunoblot analysis revealed that sorafenib inhibited Akt, MEK and ERK phosphorylation, and this effect correlated with inhibition of total Akt and total MEK, while total ERK levels remained unchanged. Sorafenib 34-43 AKT serine/threonine kinase 1 Homo sapiens 54-57 29538717-8 2018 Immunoblot analysis revealed that sorafenib inhibited Akt, MEK and ERK phosphorylation, and this effect correlated with inhibition of total Akt and total MEK, while total ERK levels remained unchanged. Sorafenib 34-43 AKT serine/threonine kinase 1 Homo sapiens 140-143 29538717-11 2018 Taken together, our results suggest that sorafenib suppresses DT proliferation and invasion via inhibition of Ras/MEK/ERK and PI3K/Akt/mTOR signaling pathways with additional effects on translation. Sorafenib 41-50 AKT serine/threonine kinase 1 Homo sapiens 131-134 30043734-10 2018 More importantly, SESN2 knockdown impaired sorafenib-induced AKT activation in HCC cells. Sorafenib 43-52 AKT serine/threonine kinase 1 Homo sapiens 61-64 30043734-11 2018 Conclusion SESN2 up-regulation conferred primary resistance to sorafenib by activating AKT in HCC cells. Sorafenib 63-72 AKT serine/threonine kinase 1 Homo sapiens 87-90 29881824-8 2018 Overexpression of constitutively activated AKT reverses the effect of knockdown of IGF1R in sensitizing HCC cells to treatment with sorafenib. Sorafenib 132-141 AKT serine/threonine kinase 1 Homo sapiens 43-46 29360358-2 2018 Activation of phosphatidylinositol 3-kinase-Akt-mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway was involved in the development of HCC and acquired resistance to sorafenib. Sorafenib 178-187 AKT serine/threonine kinase 1 Homo sapiens 44-47 29360358-2 2018 Activation of phosphatidylinositol 3-kinase-Akt-mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway was involved in the development of HCC and acquired resistance to sorafenib. Sorafenib 178-187 AKT serine/threonine kinase 1 Homo sapiens 84-87 29207150-10 2018 Western blotting results indicated that sorafenib concurrently inhibited the activities of the MAPK and AKT/mTOR pathways in thyroid cancer. Sorafenib 40-49 AKT serine/threonine kinase 1 Homo sapiens 104-107 29207150-11 2018 Autophagy was activated by sorafenib in thyroid cancer, both in vitro and in vivo, which was at least in part due to suppression of the AKT/mTOR pathway. Sorafenib 27-36 AKT serine/threonine kinase 1 Homo sapiens 136-139 29156516-0 2018 Synergistic anticancer activity of 20(S)-Ginsenoside Rg3 and Sorafenib in hepatocellular carcinoma by modulating PTEN/Akt signaling pathway. Sorafenib 61-70 AKT serine/threonine kinase 1 Homo sapiens 118-121 29251327-0 2018 Survival pathway of cholangiocarcinoma via AKT/mTOR signaling to escape RAF/MEK/ERK pathway inhibition by sorafenib. Sorafenib 106-115 AKT serine/threonine kinase 1 Homo sapiens 43-46 29251327-5 2018 Significantly decreased AKT Ser473 phosphorylation in HCC cells, and conversely enhanced phosphorylation of AKT Ser473 and mTORC2 in CCC cells, were observed with sorafenib treatment. Sorafenib 163-172 AKT serine/threonine kinase 1 Homo sapiens 24-27 29251327-5 2018 Significantly decreased AKT Ser473 phosphorylation in HCC cells, and conversely enhanced phosphorylation of AKT Ser473 and mTORC2 in CCC cells, were observed with sorafenib treatment. Sorafenib 163-172 AKT serine/threonine kinase 1 Homo sapiens 108-111 29251327-8 2018 Simultaneous administration of everolimus to suppress activated mTORC1 in RBE cells revealed that combined everolimus and sorafenib treatment under mTORC2 disassembly could enhance growth inhibition through the suppression of both sorafenib- and everolimus-dependent AKT Ser473 phosphorylation in addition to the inhibition of mTORC1 phosphorylation. Sorafenib 122-131 AKT serine/threonine kinase 1 Homo sapiens 267-270 29251327-9 2018 Prevention of escape by AKT/mTOR signaling from the RAF/MEK/ERK pathway in sorafenib treatment by suppressing mTORC2 activity may lead to promising new approaches in CCC therapy. Sorafenib 75-84 AKT serine/threonine kinase 1 Homo sapiens 24-27 29156516-2 2018 However, PI3K/Akt signaling pathway is activated by Sorafenib and cross-talks with the Raf/MAPK/ERK signaling pathway, leading to drug resistance. Sorafenib 52-61 AKT serine/threonine kinase 1 Homo sapiens 14-17 29156516-4 2018 Hence, we aim to examine the synergistic anticancer activity of 20(S)-Ginsenoside Rg3 and Sorafenib via modulation of PTEN/Akt signaling pathway. Sorafenib 90-99 AKT serine/threonine kinase 1 Homo sapiens 123-126 29156516-8 2018 The levels of PTEN, Bax and cleaved caspase-3 expression increased, while the levels of phospho-PDK1 and phospho-Akt expression decreased by the treatment of Sorafenib combined with 20(S)-Ginsenoside Rg3. Sorafenib 158-167 AKT serine/threonine kinase 1 Homo sapiens 113-116 29156516-10 2018 The results demonstrated the synergistic anticancer activity of 20(S)-Ginsenoside Rg3 and Sorafenib in HCC by modulating PTEN/Akt signaling pathway. Sorafenib 90-99 AKT serine/threonine kinase 1 Homo sapiens 126-129 29152112-5 2017 In addition, the present study demonstrated that sorafenib treatment induces activation of Akt, probably as a mechanism of resistance, whereas capsaicin inhibits Akt providing a possible pathway whereby capsaicin sensitizes to sorafenib in HCC cells. Sorafenib 49-58 AKT serine/threonine kinase 1 Homo sapiens 91-94 29021381-4 2017 Results from the initial study demonstrated that sorafenib treatment significantly decreased E-cadherin (P < 0.05) levels but significantly increased matrix metallopeptidase 9 (MMP9) levels (P < 0.01) in A549/SRFres tumors, whereas expression levels of phospho-protein kinase B (AKT), phospho-focal adhesion kinase (FAK), and phospho-Src were elevated in sorafenib-treated A549 and A549/SRFres tumors. Sorafenib 49-58 AKT serine/threonine kinase 1 Homo sapiens 285-288 29021381-7 2017 Although the sorafenib-dasatinib combination effectively inhibited Src and AKT phosphorylation, it did not block the Y576/577-FAK phosphorylation, nor did it decrease vimentin protein expression; unexpectedly, it increased Y397-FAK phosphorylation and MMP9 protein expression in tumors. Sorafenib 13-22 AKT serine/threonine kinase 1 Homo sapiens 75-78 28276313-0 2017 Inhibition of MMP-2 Expression Enhances the Antitumor Effect of Sorafenib in Hepatocellular Carcinoma by Suppressing the PI3K/AKT/mTOR Pathway. Sorafenib 64-73 AKT serine/threonine kinase 1 Homo sapiens 126-129 28687354-7 2017 Additionally, the combination of aspirin and sorafenib showed synergetic effects via inhibiting mTORC1 signaling and the PI3K/AKT, MAPK/ERK pathways. Sorafenib 45-54 AKT serine/threonine kinase 1 Homo sapiens 126-129 28934275-0 2017 Activation of phosphatidylinositol 3-kinase/AKT/snail signaling pathway contributes to epithelial-mesenchymal transition-induced multi-drug resistance to sorafenib in hepatocellular carcinoma cells. Sorafenib 154-163 AKT serine/threonine kinase 1 Homo sapiens 44-47 28934275-3 2017 The activation of AKT by sorafenib is thought to be responsible for the development of these characteristics. Sorafenib 25-34 AKT serine/threonine kinase 1 Homo sapiens 18-21 28934275-10 2017 Two sorafenib-resistant HCC cell lines, established from human HCC HepG2 and Huh7 cells, were refractory to sorafenib-induced growth inhibition but were sensitive to MK-2206, a novel allosteric AKT inhibitor. Sorafenib 4-13 AKT serine/threonine kinase 1 Homo sapiens 194-197 28934275-11 2017 Thus, the combination of sorafenib and MK-2206 led to significant reversion of the EMT phenotype and P-gp-mediated MDR by downregulating phosphorylated AKT. Sorafenib 25-34 AKT serine/threonine kinase 1 Homo sapiens 152-155 28934275-12 2017 These findings underscore the significance of EMT, MDR and enhanced PI3K/AKT signaling in sorafenib-resistant HCC cells. Sorafenib 90-99 AKT serine/threonine kinase 1 Homo sapiens 73-76 28746469-10 2017 Additionally, the phosphorylation levels of AKT, mTOR and MAPK as well as the expression levels of MMP-2 and MMP-9 were all decreased by a single treatment of IL-27 or sorafenib, and further decreased by the combined treatment of these two drugs. Sorafenib 168-177 AKT serine/threonine kinase 1 Homo sapiens 44-47 28536078-0 2017 AKT is critically involved in the antagonism of BRAF inhibitor sorafenib against dabrafenib in colorectal cancer cells harboring both wild-type and mutant (V600E) BRAF genes. Sorafenib 63-72 AKT serine/threonine kinase 1 Homo sapiens 0-3 28536078-8 2017 Moreover, we found that sorafenib reversed dabrafenib inhibition of AKT in HT-29 cells, and phosphatidylinositol-3-kinase (PI3K) inhibitor GDC0941 significantly restored this antagonistic effect when combined with dabrafenib and sorafenib, indicating that AKT is critically involved in this antagonism. Sorafenib 24-33 AKT serine/threonine kinase 1 Homo sapiens 68-71 28536078-9 2017 Collectively, we found that significant antagonism was observed when dabrafenib was combined with sorafenib in colorectal cancer cells harboring heterozygous genotype of BRAF and AKT is critically involved in this antagonism. Sorafenib 98-107 AKT serine/threonine kinase 1 Homo sapiens 179-182 28344323-6 2017 Recent studies have revealed that in addition to the primary resistance, several mechanisms are underlying the acquired resistance to sorafenib, such as crosstalk involving PI3K/Akt and JAK-STAT pathways, the activation of hypoxia-inducible pathways, and epithelial-mesenchymal transition. Sorafenib 134-143 AKT serine/threonine kinase 1 Homo sapiens 178-181 28903416-7 2017 786-O RCC cells secrete high IL-6 levels after low dose stimulation with the TKIs sorafenib, sunitinib and pazopanib, inducing activation of AKT-mTOR pathway, NFkappaB, HIF-2alpha and VEGF expression. Sorafenib 82-91 AKT serine/threonine kinase 1 Homo sapiens 141-144 28622037-0 2017 Inhibition of the AKT/mTOR Pathway Augments the Anticancer Effects of Sorafenib in Thyroid Cancer. Sorafenib 70-79 AKT serine/threonine kinase 1 Homo sapiens 18-21 28622037-8 2017 RESULTS: The results indicate that sorafenib simultaneously inhibited the activities of the MAPK and PI3K/AKT/mTOR pathways in thyroid cancer cells. Sorafenib 35-44 AKT serine/threonine kinase 1 Homo sapiens 106-109 28622037-10 2017 Sorafenib in combination with PI3K/AKT/mTOR inhibition by NVP-BEZ235 or AKT siRNA enhanced apoptosis and proliferation suppression. Sorafenib 0-9 AKT serine/threonine kinase 1 Homo sapiens 72-75 28622037-11 2017 CONCLUSIONS: The evidence of this study suggests that a combinatorial approach that inhibits both the MAPK and PI3K/AKT/mTOR pathways exerts a greater antitumor effect than sorafenib alone in thyroid cancer cell lines. Sorafenib 173-182 AKT serine/threonine kinase 1 Homo sapiens 116-119 28164434-0 2017 Dual inhibition of Akt and c-Met as a second-line therapy following acquired resistance to sorafenib in hepatocellular carcinoma cells. Sorafenib 91-100 AKT serine/threonine kinase 1 Homo sapiens 19-22 27807662-0 2017 C2-ceramide enhances sorafenib-induced caspase-dependent apoptosis via PI3K/AKT/mTOR and Erk signaling pathways in HCC cells. Sorafenib 21-30 AKT serine/threonine kinase 1 Homo sapiens 76-79 28164434-5 2017 In this study, sorafenib-resistant HCC cells generated from sorafenib-sensitive human HCC cells were shown to overproduce hepatocyte growth factor (HGF) and overexpress c-Met kinase and its phosphorylated form, leading to the activation of Akt and ERK (extracellular signaling-regulated kinase) pathways. Sorafenib 15-24 AKT serine/threonine kinase 1 Homo sapiens 240-243 28164434-5 2017 In this study, sorafenib-resistant HCC cells generated from sorafenib-sensitive human HCC cells were shown to overproduce hepatocyte growth factor (HGF) and overexpress c-Met kinase and its phosphorylated form, leading to the activation of Akt and ERK (extracellular signaling-regulated kinase) pathways. Sorafenib 60-69 AKT serine/threonine kinase 1 Homo sapiens 240-243 28164434-7 2017 Akt inhibitors, a class of second-line therapeutic drugs under investigation for treating HCC in clinical trials, enhanced the effects of sorafenib, but also activated the c-Met pathway in sorafenib-resistant cells. Sorafenib 138-147 AKT serine/threonine kinase 1 Homo sapiens 0-3 28164434-7 2017 Akt inhibitors, a class of second-line therapeutic drugs under investigation for treating HCC in clinical trials, enhanced the effects of sorafenib, but also activated the c-Met pathway in sorafenib-resistant cells. Sorafenib 189-198 AKT serine/threonine kinase 1 Homo sapiens 0-3 28164434-10 2017 These results provide strong evidence for further investigation on the clinical utility of dual inhibition of Akt and c-Met, particularly MK2206 and capmatinib, as a second-line therapy for advanced HCC that has acquired resistance to sorafenib. Sorafenib 235-244 AKT serine/threonine kinase 1 Homo sapiens 110-113 27807662-7 2017 Combination treatment of sorafenib and C2-ceramide inhibited obviously cell growth and proliferation via PI3K/AKT/mTOR and Erk signaling pathways. Sorafenib 25-34 AKT serine/threonine kinase 1 Homo sapiens 110-113 27496136-4 2016 Herein, we show that SF1126 (pan PI3K/BRD4 inhibitor) as single agent or in combination with sorafenib inhibited proliferation, cell cycle, apoptosis, and multiple key enzymes in PI3K/AKT/mTOR and Ras/Raf/MAPK pathway in Hep3B, HepG2, SK-Hep1, and Huh7 HCC cell lines. Sorafenib 93-102 AKT serine/threonine kinase 1 Homo sapiens 184-187 27873490-7 2017 EGF activated epidermal growth factor receptor (EGFR) and triggered resistance to sunitinib, E7080, vandetanib, and sorafenib by transducing bypass survival signaling through ERK and AKT. Sorafenib 116-125 AKT serine/threonine kinase 1 Homo sapiens 183-186 27816967-7 2016 In sorafenib-resistant cells, ubenimex inhibited the Akt signaling pathway that regulates autophagy. Sorafenib 3-12 AKT serine/threonine kinase 1 Homo sapiens 53-56 27816967-8 2016 In summary, lipophagy participates in sorafenib-resistance of RCC, which could be reversed by interventions targeting the Akt pathway. Sorafenib 38-47 AKT serine/threonine kinase 1 Homo sapiens 122-125 27877053-8 2016 The sorafenib and vorinostat combination sustained the IGF-1R-, AKT-, and mitogen-activated protein kinase-dependent signaling pathways. Sorafenib 4-13 AKT serine/threonine kinase 1 Homo sapiens 64-67 27689326-6 2016 Infection of Ad5-AlncRNA into sorafenib-resistant HCC cells blocked the function of miRNAs, and sequentially inhibited the downregulation of PTEN and activation of AKT. Sorafenib 30-39 AKT serine/threonine kinase 1 Homo sapiens 164-167 27167344-0 2016 Des-gamma-carboxy prothrombin antagonizes the effects of Sorafenib on human hepatocellular carcinoma through activation of the Raf/MEK/ERK and PI3K/Akt/mTOR signaling pathways. Sorafenib 57-66 AKT serine/threonine kinase 1 Homo sapiens 148-151 26299635-0 2016 Combinatorial anticancer effects of curcumin and sorafenib towards thyroid cancer cells via PI3K/Akt and ERK pathways. Sorafenib 49-58 AKT serine/threonine kinase 1 Homo sapiens 97-100 27248172-9 2016 Taken together, our study revealed a novel mechanism in microenvironment influence on sorafenib sensitivity in AML with FLT3-ITD mutation that was caused by activating integrin alphavbeta3/PI3K/Akt/GSK3beta/beta-catenin pathway. Sorafenib 86-95 AKT serine/threonine kinase 1 Homo sapiens 194-197 26711788-8 2016 Based on these results, we conclude that resistance to sorafenib is associated with weak ERK signaling and strong Akt signaling in LCSCs. Sorafenib 55-64 AKT serine/threonine kinase 1 Homo sapiens 114-117 27167344-8 2016 Our results indicate that DCP antagonizes the inhibitory effects of Sorafenib on HCC through activation of the Ras/Raf/MEK/ERK and Ras/PI3K/Akt/mTOR signaling pathways. Sorafenib 68-77 AKT serine/threonine kinase 1 Homo sapiens 140-143 27152946-4 2016 The synergistic effects of alpha-Mangostin and Sorafenib were associated with enhanced inhibition of activated AKT and ERK, induced ER stress, and reduced autophagy, eventually leading to apoptosis. Sorafenib 47-56 AKT serine/threonine kinase 1 Homo sapiens 111-114 26629768-0 2016 Sorafenib induces autophagic cell death and apoptosis in hepatic stellate cell through the JNK and Akt signaling pathways. Sorafenib 0-9 AKT serine/threonine kinase 1 Homo sapiens 99-102 26629768-12 2016 Finally, sorafenib induced programmed cell death by attenuation and activation of Akt/mTOR/p70S6K and JNK signaling. Sorafenib 9-18 AKT serine/threonine kinase 1 Homo sapiens 82-85 26782953-0 2016 Bufalin enhances anti-angiogenic effect of sorafenib via AKT/VEGF signaling. Sorafenib 43-52 AKT serine/threonine kinase 1 Homo sapiens 57-60 26782953-15 2016 Taken together, our findings demonstrated for the first time that bufalin can enhance anti-angiogenic effect of sorafenib via modulating the AKT/VEGF signaling pathway. Sorafenib 112-121 AKT serine/threonine kinase 1 Homo sapiens 141-144 26179270-6 2016 The inception of sorafenib for HCC systemic therapy and the understanding involved of cancer therapy have led to an enhanced focus of the PI3-k/Akt/mTOR pathway as a potential area of targeting including pan and isoform-specific PI3-K inhibitors, Akt blockade, and mTOR suppression. Sorafenib 17-26 AKT serine/threonine kinase 1 Homo sapiens 144-147 26179270-6 2016 The inception of sorafenib for HCC systemic therapy and the understanding involved of cancer therapy have led to an enhanced focus of the PI3-k/Akt/mTOR pathway as a potential area of targeting including pan and isoform-specific PI3-K inhibitors, Akt blockade, and mTOR suppression. Sorafenib 17-26 AKT serine/threonine kinase 1 Homo sapiens 247-250 27095937-7 2016 Moreover, sorafenib and pemetrexed demonstrated stronger synergism, demonstrating that inhibiting the Ras/Raf/Mek/Erk and Ras/PI3K/Akt pathways concurrently may achieve improved antitumor effects. Sorafenib 10-19 AKT serine/threonine kinase 1 Homo sapiens 131-134 26257239-0 2015 Sorafenib enriches epithelial cell adhesion molecule-positive tumor initiating cells and exacerbates a subtype of hepatocellular carcinoma through TSC2-AKT cascade. Sorafenib 0-9 AKT serine/threonine kinase 1 Homo sapiens 152-155 26257239-4 2015 The TSC2-AKT cascade mediates this sorafenib resistance. Sorafenib 35-44 AKT serine/threonine kinase 1 Homo sapiens 9-12 26257239-5 2015 In response to sorafenib treatment, formation of the TSC1/2 complex is enhanced, causing increased phosphorylation of AKT, which contributes to up-regulation of "stemness"-related genes in epithelial cell adhesion molecule-positive cells and enhancement of tumorigenicity. Sorafenib 15-24 AKT serine/threonine kinase 1 Homo sapiens 118-121 26311740-0 2015 MiR-21 mediates sorafenib resistance of hepatocellular carcinoma cells by inhibiting autophagy via the PTEN/Akt pathway. Sorafenib 16-25 AKT serine/threonine kinase 1 Homo sapiens 108-111 26311740-2 2015 Recent studies indicate that activated Akt contributes to the acquired resistance to sorafenib, and miR-21 dysregulates phosphatase and tensin homolog (PTEN), which inhibits Akt activation. Sorafenib 85-94 AKT serine/threonine kinase 1 Homo sapiens 39-42 26311740-4 2015 Akt and its downstream factors were highly activated and/or upregulated in sorafenib-resistant cells. Sorafenib 75-84 AKT serine/threonine kinase 1 Homo sapiens 0-3 26311740-7 2015 Exposure of HCC cells to sorafenib led to an increase in miR-21 expression, a decrease in PTEN expression and sequential Akt activation. Sorafenib 25-34 AKT serine/threonine kinase 1 Homo sapiens 121-124 26311740-11 2015 We conclude that miR-21 participates in the acquired resistance of sorafenib by suppresing autophagy through the Akt/PTEN pathway. Sorafenib 67-76 AKT serine/threonine kinase 1 Homo sapiens 113-116 26206949-10 2015 Sorafenib markedly inhibited the HBx-enhanced AR activity through activating the SHP-1 phosphatase, which antagonized the activation of Akt/GSK3beta and c-Src by HBx. Sorafenib 0-9 AKT serine/threonine kinase 1 Homo sapiens 136-139 26381511-2 2015 The activation of Akt by sorafenib is thought to be responsible for this resistance. Sorafenib 25-34 AKT serine/threonine kinase 1 Homo sapiens 18-21 26381511-6 2015 This effect was at least partially due to the ability of bufalin to inhibit Akt activation by sorafenib. Sorafenib 94-103 AKT serine/threonine kinase 1 Homo sapiens 76-79 26381511-11 2015 Thus, Bufalin reversed acquired resistance to sorafenib by downregulating phosphorylated Akt in an ER-stress-dependent manner via the IRE1 pathway. Sorafenib 46-55 AKT serine/threonine kinase 1 Homo sapiens 89-92 25862630-0 2015 Enhanced sensitivity to sorafenib by inhibition of Akt1 expression in human renal cell carcinoma ACHN cells both in vitro and in vivo. Sorafenib 24-33 AKT serine/threonine kinase 1 Homo sapiens 51-55 25862630-1 2015 To investigate whether antitumor activity of sorafenib, a potential molecular-targeted agent against RCC is enhanced by silencing Akt1 in a human RCC ACHN model. Sorafenib 45-54 AKT serine/threonine kinase 1 Homo sapiens 130-134 25862630-3 2015 Changes in several phenotypes of ACHN/sh-Akt1 following treatment with sorafenib were compared with those of ACHN transfected with control vector alone (ACHN/C) both in vitro and in vivo. Sorafenib 71-80 AKT serine/threonine kinase 1 Homo sapiens 41-45 25862630-5 2015 Furthermore, treatment with Akt1 inhibitor, A-674563 also resulted in the significantly enhanced sensitivity of parental ACHN to sorafenib. Sorafenib 129-138 AKT serine/threonine kinase 1 Homo sapiens 28-32 25862630-6 2015 Treatment of ACHN/sh-Akt1 with sorafenib, but not that of ACHN/C, induced marked downregulation of antiapoptotic proteins, including Bcl-2, Bcl-xL, and c-Myc. Sorafenib 31-40 AKT serine/threonine kinase 1 Homo sapiens 21-25 25768669-7 2015 Sorafenib blocked RET, AKT, and ERK1/2 phosphorylation, whereas cabozantinib blocked RET and AKT phosphorylation. Sorafenib 0-9 AKT serine/threonine kinase 1 Homo sapiens 23-26 25416439-0 2015 Arsenic trioxide potentiates the anti-cancer activities of sorafenib against hepatocellular carcinoma by inhibiting Akt activation. Sorafenib 59-68 AKT serine/threonine kinase 1 Homo sapiens 116-119 25416439-1 2015 Sorafenib is the standard first-line systemic drug for advanced hepatocellular carcinoma (HCC), but it also induces the activation of Akt, which contributes to the mechanisms for the resistance to sorafenib. Sorafenib 0-9 AKT serine/threonine kinase 1 Homo sapiens 134-137 25416439-1 2015 Sorafenib is the standard first-line systemic drug for advanced hepatocellular carcinoma (HCC), but it also induces the activation of Akt, which contributes to the mechanisms for the resistance to sorafenib. Sorafenib 197-206 AKT serine/threonine kinase 1 Homo sapiens 134-137 25416439-4 2015 The results have demonstrated that ATO synergized with sorafenib to inhibit the proliferation and promote the apoptosis of HCC cells by diminishing the increased activation of Akt by sorafenib. Sorafenib 55-64 AKT serine/threonine kinase 1 Homo sapiens 176-179 25416439-4 2015 The results have demonstrated that ATO synergized with sorafenib to inhibit the proliferation and promote the apoptosis of HCC cells by diminishing the increased activation of Akt by sorafenib. Sorafenib 183-192 AKT serine/threonine kinase 1 Homo sapiens 176-179 25416439-5 2015 ATO was shown to inhibit the expression or activation of Akt downstream factors, including glycogen synthase kinase (GSK)-3beta, mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase (S6K), and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1), which regulate cell apoptosis and were upregulated or activated by sorafenib. Sorafenib 344-353 AKT serine/threonine kinase 1 Homo sapiens 57-60 25879531-14 2015 Sorafenib treatment caused a rapid inhibition of various MAP kinases in addition to inhibiting AKT and receptor tyrosine kinases. Sorafenib 0-9 AKT serine/threonine kinase 1 Homo sapiens 95-98 26097873-0 2015 Sorafenib induces cathepsin B-mediated apoptosis of bladder cancer cells by regulating the Akt/PTEN pathway. Sorafenib 0-9 AKT serine/threonine kinase 1 Homo sapiens 91-94 26097873-1 2015 The Akt inhibitor, perifosine, enhances the sorafenib-induced cytotoxicity against bladder cancer cells. Sorafenib 44-53 AKT serine/threonine kinase 1 Homo sapiens 4-7 26097873-8 2015 Moreover, we found that cathepsin B enzymatic activity, induced by sorafenib, is dependent on its dephosphorylation via PTEN activation and Akt inactivation. Sorafenib 67-76 AKT serine/threonine kinase 1 Homo sapiens 140-143 26097873-10 2015 In addition, the Akt inhibitor perifosine increased the sensitivity of bladder cancer cells to sorafenib-induced cytotoxicity. Sorafenib 95-104 AKT serine/threonine kinase 1 Homo sapiens 17-20 26097873-11 2015 Overall, our results show that apoptotic cell death induced by sorafenib in bladder cancer cells is dependent on cathepsin B activity and involved PTEN and Akt signaling pathways. Sorafenib 63-72 AKT serine/threonine kinase 1 Homo sapiens 156-159 26097873-12 2015 The Akt inhibitor perifosine increased the cytotoxic effects of sorafenib in bladder cancer cells. Sorafenib 64-73 AKT serine/threonine kinase 1 Homo sapiens 4-7 25494980-9 2014 The combined treatment of Casodex reverted the observed resistance to Sorafenib both on cell viability and on Akt activation, whereas it did not modify the response to Sunitinib. Sorafenib 70-79 AKT serine/threonine kinase 1 Homo sapiens 110-113 25778319-0 2015 Sorafenib inhibits liver cancer growth by decreasing mTOR, AKT, and PI3K expression. Sorafenib 0-9 AKT serine/threonine kinase 1 Homo sapiens 59-62 25778319-1 2015 PURPOSE: The purpose of this study was to determine the impact of sorafenib on PI3K/AKT/mTOR signaling pathway and to further define its mechanism for treating hepatocellular carcinoma (HCC). Sorafenib 66-75 AKT serine/threonine kinase 1 Homo sapiens 84-87 25778319-4 2015 RESULTS: Human SMMC-7721 hepatic tumor cells exposed to sorafenib had decreased expression of PI3K/mTOR/AKT. Sorafenib 56-65 AKT serine/threonine kinase 1 Homo sapiens 104-107 25778319-5 2015 CONCLUSION: Sorafenib appears to inhibit hepatic tumor growth by downregulating PI3k/Akt/mTOR signaling pathway. Sorafenib 12-21 AKT serine/threonine kinase 1 Homo sapiens 85-88 25491250-11 2014 Preliminary analysis of total AKT and ERK1/2 levels in plasma EVs from patients with NSCLC before and after sorafenib/metformin treatment (n=12) shows a significant decrease in AKT levels among patients with a favourable treatment response (p<0.005). Sorafenib 108-117 AKT serine/threonine kinase 1 Homo sapiens 30-33 25491250-11 2014 Preliminary analysis of total AKT and ERK1/2 levels in plasma EVs from patients with NSCLC before and after sorafenib/metformin treatment (n=12) shows a significant decrease in AKT levels among patients with a favourable treatment response (p<0.005). Sorafenib 108-117 AKT serine/threonine kinase 1 Homo sapiens 177-180 25096647-9 2014 In conclusion, this study demonstrates that miR-222 can promote cell proliferation, migration and invasion, and decrease cell apoptosis, as well as enhance the resistance of HCC cells to sorafenib miR-222 through activating the PI3K/AKT signaling pathway. Sorafenib 187-196 AKT serine/threonine kinase 1 Homo sapiens 233-236 24571452-0 2014 ABT-263 enhances sorafenib-induced apoptosis associated with Akt activity and the expression of Bax and p21((CIP1/WAF1)) in human cancer cells. Sorafenib 17-26 AKT serine/threonine kinase 1 Homo sapiens 61-64 25070581-0 2014 Activation of phosphatidylinositol 3-kinase/Akt signaling mediates sorafenib-induced invasion and metastasis in hepatocellular carcinoma. Sorafenib 67-76 AKT serine/threonine kinase 1 Homo sapiens 44-47 25070581-3 2014 Yet, little is known concerning the role of the PI3K/Akt/Snail-dependent pathway in sorafenib-induced invasion and metastasis of hepatic carcinoma (HCC). Sorafenib 84-93 AKT serine/threonine kinase 1 Homo sapiens 53-56 25070581-10 2014 Importantly, sorafenib enhanced PI3K and Akt activation and upregulation of the expression of transcription factor Snail, a critical EMT mediator. Sorafenib 13-22 AKT serine/threonine kinase 1 Homo sapiens 41-44 25070581-11 2014 The upregulation of transcription factor Snail expression by sorafenib may be related to activation of the PI3K/AKT signaling pathway. Sorafenib 61-70 AKT serine/threonine kinase 1 Homo sapiens 112-115 25070581-12 2014 The PI3K/Akt/Snail-dependent pathway may mediate the pro-invasive and pro-metastatic effects of sorafenib on HCC by inducing EMT. Sorafenib 96-105 AKT serine/threonine kinase 1 Homo sapiens 9-12 24571452-9 2014 ABT-263 plus sorafenib significantly decreased Akt activity, which was, at least partly, involved in its effect on apoptosis. Sorafenib 13-22 AKT serine/threonine kinase 1 Homo sapiens 47-50 24571452-12 2014 CONCLUSION AND IMPLICATIONS: The anti-tumour activity of ABT-263 plus sorafenib may involve the induction of intrinsic cell apoptosis via inhibition of Akt, and reduced Bax and p21 expression. Sorafenib 70-79 AKT serine/threonine kinase 1 Homo sapiens 152-155 24705351-0 2014 Inhibition of Akt reverses the acquired resistance to sorafenib by switching protective autophagy to autophagic cell death in hepatocellular carcinoma. Sorafenib 54-63 AKT serine/threonine kinase 1 Homo sapiens 14-17 24705351-2 2014 Activation of Akt is thought to be responsible for mediating the acquired resistance to sorafenib. Sorafenib 88-97 AKT serine/threonine kinase 1 Homo sapiens 14-17 24705351-5 2014 Sustained exposure to sorafenib activated Akt via the feedback loop of mTOR but independent of protein phosphatase 2A in HCC cells. Sorafenib 22-31 AKT serine/threonine kinase 1 Homo sapiens 42-45 24705351-7 2014 However, rapamycin did not show a synergistic effect with sorafenib to inhibit cell proliferation, while it also activated Akt via a feedback mechanism in sorafenib-resistant HCC cells. Sorafenib 155-164 AKT serine/threonine kinase 1 Homo sapiens 123-126 24705351-8 2014 Inhibition of Akt reversed the acquired resistance to sorafenib by switching autophagy from a cytoprotective role to a death-promoting mechanism in the sorafenib-resistant HCC cells. Sorafenib 54-63 AKT serine/threonine kinase 1 Homo sapiens 14-17 24705351-8 2014 Inhibition of Akt reversed the acquired resistance to sorafenib by switching autophagy from a cytoprotective role to a death-promoting mechanism in the sorafenib-resistant HCC cells. Sorafenib 152-161 AKT serine/threonine kinase 1 Homo sapiens 14-17 24705351-9 2014 Akt inhibition by GDC0068 synergized with sorafenib to suppress the growth of sorafenib-resistant HCC tumors that possessed the sorafenib-resistant feature in vivo. Sorafenib 42-51 AKT serine/threonine kinase 1 Homo sapiens 0-3 24705351-9 2014 Akt inhibition by GDC0068 synergized with sorafenib to suppress the growth of sorafenib-resistant HCC tumors that possessed the sorafenib-resistant feature in vivo. Sorafenib 78-87 AKT serine/threonine kinase 1 Homo sapiens 0-3 24705351-9 2014 Akt inhibition by GDC0068 synergized with sorafenib to suppress the growth of sorafenib-resistant HCC tumors that possessed the sorafenib-resistant feature in vivo. Sorafenib 78-87 AKT serine/threonine kinase 1 Homo sapiens 0-3 24817927-6 2014 The decreased anti-tumor effect of sorafenib was rescued by chemical inhibition of ERK and AKT. Sorafenib 35-44 AKT serine/threonine kinase 1 Homo sapiens 91-94 24817927-7 2014 When TGF-beta-sensitized cells were treated with sorafenib plus VPA, the levels of phosphorylated ERK and AKT were considerably suppressed and the numbers of dead cells were increased by 3.7-5.7-fold compared with those exposed to sorafenib alone (P<0.05). Sorafenib 49-58 AKT serine/threonine kinase 1 Homo sapiens 106-109 24817927-9 2014 Collectively, TGF-beta/ERK/AKT signaling might play a critical role in sorafenib resistance in hepatoma cells, and combination treatment with VPA may be effective against this drug resistance. Sorafenib 71-80 AKT serine/threonine kinase 1 Homo sapiens 27-30 23543326-0 2014 Sorafenib enhances proteasome inhibitor-induced cell death via inactivation of Akt and stress-activated protein kinases. Sorafenib 0-9 AKT serine/threonine kinase 1 Homo sapiens 79-82 23543326-14 2014 Sorafenib induced down-regulation of Akt synergistically in combination with proteasome inhibitors in Huh7. Sorafenib 0-9 AKT serine/threonine kinase 1 Homo sapiens 37-40 23543326-17 2014 CONCLUSIONS: Sorafenib enhances the anti-proliferative effect of proteasome inhibitors in part by inactivating the Akt signaling pathway and modulating stress-activated protein kinases. Sorafenib 13-22 AKT serine/threonine kinase 1 Homo sapiens 115-118 24563371-11 2014 Further study demonstrated that NORE1A was capable of sensitising cancer cells to sorafenib-induced apoptosis via the activation of the Mst-1/Akt pathway. Sorafenib 82-91 AKT serine/threonine kinase 1 Homo sapiens 142-145 24696725-7 2014 Western blotting results showed that those 3 HMT genes knockdown alone or sorafenib treatments alone both induce AKT/ERK activation. Sorafenib 74-83 AKT serine/threonine kinase 1 Homo sapiens 113-116 24696725-8 2014 However, combination treatment with sorafenib and silencing of C17ORF49 or SETD4 downregulated AKT phosphorylation and hence induced HCC cells death. Sorafenib 36-45 AKT serine/threonine kinase 1 Homo sapiens 95-98 23812726-7 2013 The inhibition of kinase activation using multi-targeted kinase inhibitors, sorafenib and sunitinib led to significant cell growth inhibition and apoptosis induction via suppression of Erk1/2 and Akt activation, whereas drugs with specificity to a single kinase showed less potency. Sorafenib 76-85 AKT serine/threonine kinase 1 Homo sapiens 196-199 25057499-0 2014 Hepatic stellate cell coculture enables sorafenib resistance in Huh7 cells through HGF/c-Met/Akt and Jak2/Stat3 pathways. Sorafenib 40-49 AKT serine/threonine kinase 1 Homo sapiens 93-96 25057499-6 2014 RESULTS: LX2 coculture significantly induced sorafenib resistance in Huh7 by activating p-Akt that led to reactivation of p-ERK. Sorafenib 45-54 AKT serine/threonine kinase 1 Homo sapiens 90-93 25057499-8 2014 The inhibition of p-Akt blocked sorafenib resistance caused by LX2 coculture. Sorafenib 32-41 AKT serine/threonine kinase 1 Homo sapiens 20-23 25057499-12 2014 CONCLUSIONS: HSC-LX2 coculture induced sorafenib resistance in Huh7 through multiple pathways: HGF/c-Met/Akt pathway and Jak2/Stat3 pathway. Sorafenib 39-48 AKT serine/threonine kinase 1 Homo sapiens 105-108 23471579-9 2013 Additionally, activation of the TGF-beta- and PI3K/Akt-signaling pathways in HCC cells resulted in an acquired resistance to sorafenib, whereas blocking activation of the TGF-beta pathway overcame miR-216a/217-induced sorafenib resistance and prevented tumor metastases in HCC. Sorafenib 125-134 AKT serine/threonine kinase 1 Homo sapiens 51-54 23877009-1 2013 The present studies were undertaken to determine whether the multikinase inhibitors sorafenib/regorafenib cooperated with clinically relevant , phosphatidyl inositol 3 kinase (PI3K)-thymoma viral proto-oncogene (AKT) inhibitors to kill tumor cells. Sorafenib 84-93 AKT serine/threonine kinase 1 Homo sapiens 212-215 23877009-12 2013 Collectively our data demonstrate that the combination of sorafenib family kinase inhibitors with inhibitors of the PI3K/AKT pathway kills tumor cells in vitro and in vivo. Sorafenib 58-67 AKT serine/threonine kinase 1 Homo sapiens 121-124 23682582-8 2013 Furthermore, sorafenib pretreatment led to decreased phosphorylation levels of extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) in SMMC-7721 cells. Sorafenib 13-22 AKT serine/threonine kinase 1 Homo sapiens 145-148 23463670-0 2013 Sorafenib induces endometrial carcinoma apoptosis by inhibiting Elk-1-dependent Mcl-1 transcription and inducing Akt/GSK3beta-dependent protein degradation. Sorafenib 0-9 AKT serine/threonine kinase 1 Homo sapiens 113-116 23463670-9 2013 Furthermore, sorafenib reduced the stability of the Mcl-1 protein by enhancing its ubiquitination and degradation by the proteasome via the AKT/GSK3beta and the ERK pathways. Sorafenib 13-22 AKT serine/threonine kinase 1 Homo sapiens 140-143 23898367-7 2013 Several mechanisms are involved in the acquired resistance to sorafenib, such as crosstalks involving PI3K/Akt and JAK-STAT pathways, hypoxia-inducible pathways, epithelial-mesenchymal transition, etc. Sorafenib 62-71 AKT serine/threonine kinase 1 Homo sapiens 107-110 23807172-0 2013 Synergistic antitumour activity of sorafenib in combination with tetrandrine is mediated by reactive oxygen species (ROS)/Akt signaling. Sorafenib 35-44 AKT serine/threonine kinase 1 Homo sapiens 122-125 23807172-9 2013 CONCLUSION: The antitumour activity of sorafenib plus tetrandrine may be attributed to the induction of the intrinsic apoptosis pathway through ROS/Akt signaling. Sorafenib 39-48 AKT serine/threonine kinase 1 Homo sapiens 148-151 23340175-9 2013 Taken together, our study demonstrates that combined treatment with Sorafenib and HS-173 has a synergistic anti-cancer effect on pancreatic cancer cells, indicating that simultaneously targeting the RAF/MEK and PI3K/AKT pathways can induce a synergistic inhibitory effect on pancreatic cancers in which both pathways are activated. Sorafenib 68-77 AKT serine/threonine kinase 1 Homo sapiens 216-219 22973961-8 2013 Moreover, sorafenib reduced Akt/ERK phosphorylation in erlotinib-resistant cells, associated with significant RKIP up-regulation. Sorafenib 10-19 AKT serine/threonine kinase 1 Homo sapiens 28-31 23620775-0 2013 Sorafenib inhibits lymphoma xenografts by targeting MAPK/ERK and AKT pathways in tumor and vascular cells. Sorafenib 0-9 AKT serine/threonine kinase 1 Homo sapiens 65-68 23620775-2 2013 In vitro, sorafenib significantly decreased cell proliferation and phosphorylation levels of MAPK and PI3K/Akt pathways while increased apoptotic cell death. Sorafenib 10-19 AKT serine/threonine kinase 1 Homo sapiens 107-110 23620775-5 2013 Upon sorafenib treatment, endothelial and tumor cells from SU-DHL-4V, Granta-519, and KMS-11 nodules showed a potent inhibition of either phospho-ERK or phospho-AKT, whereas a concomitant inhibition of phospho-ERK and phospho-AKT was only observed in HD-MyZ nodules. Sorafenib 5-14 AKT serine/threonine kinase 1 Homo sapiens 161-164 23620775-5 2013 Upon sorafenib treatment, endothelial and tumor cells from SU-DHL-4V, Granta-519, and KMS-11 nodules showed a potent inhibition of either phospho-ERK or phospho-AKT, whereas a concomitant inhibition of phospho-ERK and phospho-AKT was only observed in HD-MyZ nodules. Sorafenib 5-14 AKT serine/threonine kinase 1 Homo sapiens 226-229 23564777-6 2013 RESULTS: When compared to the actions of either agent alone, the combination of low concentrations of sorafenib (<5 muM) and celecoxib (<20 muM) resulted in enhanced inhibition of both cell growth and AKT activation, and increased the induction of apoptosis. Sorafenib 102-111 AKT serine/threonine kinase 1 Homo sapiens 207-210 23324350-4 2013 Sorafenib reduces proliferation of glioblastoma cultures, and this effect depends, at least in part, on the inhibition of PI3K/Akt and MAPK pathways, both involved in gliomagenesis. Sorafenib 0-9 AKT serine/threonine kinase 1 Homo sapiens 127-130 23409093-6 2013 Sorafenib down-regulated the stimulatory receptor CD69 in NK cells of tumor-bearing mice, but not in tumor-free mice, and inhibited proliferation of NK92-MI cells, which is associated with the blocking of the PI3K/AKT pathway, and inhibited cytotoxicity of NK cells in response to tumor targets, which was due to impaired ERK phosphorylation. Sorafenib 0-9 AKT serine/threonine kinase 1 Homo sapiens 214-217 22261591-0 2012 PKI-587 and sorafenib targeting PI3K/AKT/mTOR and Ras/Raf/MAPK pathways synergistically inhibit HCC cell proliferation. Sorafenib 12-21 AKT serine/threonine kinase 1 Homo sapiens 37-40 22696593-5 2012 Combination with the multikinase inhibitor, sorafenib, abrogates rapamycin-induced activation of PI3K/Akt and Ras-MAPK signaling pathways. Sorafenib 44-53 AKT serine/threonine kinase 1 Homo sapiens 102-105 22261591-9 2012 However, sorafenib, as a single agent, increased AKT (Ser473) phosphorylation. Sorafenib 9-18 AKT serine/threonine kinase 1 Homo sapiens 49-52 22261591-13 2012 However, when PKI-587 and sorafenib were used in combination, they inhibited all the tested kinases in the Ras/Raf /MAPK and PI3K/AKT/mTOR pathways. Sorafenib 26-35 AKT serine/threonine kinase 1 Homo sapiens 130-133 22261591-14 2012 CONCLUSION: The combination of PKI-587 and sorafenib has the advantage over monodrug therapy on inhibition of HCC cell proliferation by blocking both PI3K/AKT/mTOR and Ras/Raf/MAPK signaling pathways. Sorafenib 43-52 AKT serine/threonine kinase 1 Homo sapiens 155-158 22265862-0 2012 Blockade of ataxia telangiectasia mutated sensitizes hepatoma cell lines to sorafenib by interfering with Akt signaling. Sorafenib 76-85 AKT serine/threonine kinase 1 Homo sapiens 106-109 22414764-9 2012 In cell lines cultured in 10% serum or treated with EGF, sorafenib alone inhibited phospho-STAT3 while it maintained or even increased phospho-ERK and/or phospho-AKT. Sorafenib 57-66 AKT serine/threonine kinase 1 Homo sapiens 162-165 22634008-6 2012 Moreover, sorafenib inhibited IFN-alpha induced oncogenic signaling of STAT3, AKT and ERK but not the activation of the tumor suppressor STAT1. Sorafenib 10-19 AKT serine/threonine kinase 1 Homo sapiens 78-81 22265862-3 2012 When hepatoma cell lines HepG2 and PLC/PRF/5 were treated with sorafenib plus ATM small inhibitory RNAs, ATM inhibitor KU55933 or caffeine, Akt signaling was suppressed and the cytotoxic effects were significantly potentiated. Sorafenib 63-72 AKT serine/threonine kinase 1 Homo sapiens 140-143 22787432-10 2012 Collectively, these findings demonstrate that CH12 interacts additively with sorafenib to strongly inhibit the tumor growth of HCC xenografts expressing EGFRvIII by enhancing the sorafenib-mediated inhibition of the MEK/ERK, phosphoinositide 3-kinase/AKT, and STAT3 pathways. Sorafenib 179-188 AKT serine/threonine kinase 1 Homo sapiens 225-254 22278289-4 2012 In PC3 cells, Src and AKT are constitutively activated and targeted by sorafenib, leading to an increase in Bim protein levels. Sorafenib 71-80 AKT serine/threonine kinase 1 Homo sapiens 22-25 22278289-5 2012 Overexpression of constitutively active AKT or knockdown of Bim protects PC3 cells from sorafenib-induced killing. Sorafenib 88-97 AKT serine/threonine kinase 1 Homo sapiens 40-43 21965734-0 2011 Fluvastatin enhances sorafenib cytotoxicity in melanoma cells via modulation of AKT and JNK signaling pathways. Sorafenib 21-30 AKT serine/threonine kinase 1 Homo sapiens 80-83 21529991-11 2011 CONCLUSIONS: These data demonstrate that sorafenib and gemcitabine synergistically interact against NSCLC cells, through suppression of Akt, c-Kit and ERK phosphorylation, induction of apoptosis and modulation of dCK, RRM1, RRM2 and RKIP gene expression. Sorafenib 41-50 AKT serine/threonine kinase 1 Homo sapiens 136-139 21734462-8 2011 However, vitamin K1 enhanced sorafenib-induced c-Met phosphorylation at Tyr-1349, a DEP-1 protein phosphatase acting site, and consequently induced phosphorylation of PI3K-Akt. Sorafenib 29-38 AKT serine/threonine kinase 1 Homo sapiens 172-175 21734462-9 2011 Both PI3K inhibitor Ly294002 as well as dominate negative Akt plasmid transfection antagonized vitamin K1 plus sorafenib actions on c-Raf phosphorylation and cell growth inhibition, suggesting that c-Met-PI3K-Akt signaling pathway mediated inhibitory c-Raf phosphorylation may play a central role in vitamin K1 plus sorafenib synergy in inhibiting HCC cell growth. Sorafenib 111-120 AKT serine/threonine kinase 1 Homo sapiens 58-61 21734462-9 2011 Both PI3K inhibitor Ly294002 as well as dominate negative Akt plasmid transfection antagonized vitamin K1 plus sorafenib actions on c-Raf phosphorylation and cell growth inhibition, suggesting that c-Met-PI3K-Akt signaling pathway mediated inhibitory c-Raf phosphorylation may play a central role in vitamin K1 plus sorafenib synergy in inhibiting HCC cell growth. Sorafenib 111-120 AKT serine/threonine kinase 1 Homo sapiens 209-212 21734462-9 2011 Both PI3K inhibitor Ly294002 as well as dominate negative Akt plasmid transfection antagonized vitamin K1 plus sorafenib actions on c-Raf phosphorylation and cell growth inhibition, suggesting that c-Met-PI3K-Akt signaling pathway mediated inhibitory c-Raf phosphorylation may play a central role in vitamin K1 plus sorafenib synergy in inhibiting HCC cell growth. Sorafenib 316-325 AKT serine/threonine kinase 1 Homo sapiens 58-61 21790999-10 2011 Treatment with sorafenib, either alone or in combination with DOX, resulted in Akt activation. Sorafenib 15-24 AKT serine/threonine kinase 1 Homo sapiens 79-82 21689083-0 2011 Multikinase inhibitor sorafenib exerts cytocidal efficacy against Non-Hodgkin lymphomas associated with inhibition of MAPK14 and AKT phosphorylation. Sorafenib 22-31 AKT serine/threonine kinase 1 Homo sapiens 129-132 21734462-0 2011 c-Met-Akt pathway-mediated enhancement of inhibitory c-Raf phosphorylation is involved in vitamin K1 and sorafenib synergy on HCC growth inhibition. Sorafenib 105-114 AKT serine/threonine kinase 1 Homo sapiens 6-9 21768474-8 2011 Sorafenib inhibited the phosphorylation of AKT, S6 ribosomal protein, and 4E-BP1 in leukemia cells. Sorafenib 0-9 AKT serine/threonine kinase 1 Homo sapiens 43-46 21205925-0 2011 Activation of phosphatidylinositol 3-kinase/Akt signaling pathway mediates acquired resistance to sorafenib in hepatocellular carcinoma cells. Sorafenib 98-107 AKT serine/threonine kinase 1 Homo sapiens 44-47 21205925-5 2011 Thorough comparisons of the molecular changes between Huh7 and resistant cells showed that the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway played a significant role in mediating acquired resistance to sorafenib in Huh7-R1 and Huh7-R2 cells. Sorafenib 216-225 AKT serine/threonine kinase 1 Homo sapiens 132-135 21205925-7 2011 In addition, ectopic expression of constitutive Akt in Huh7 demonstrated similar resistance to sorafenib. Sorafenib 95-104 AKT serine/threonine kinase 1 Homo sapiens 48-51 21205925-8 2011 The knockdown of Akt by RNA interference reversed resistance to sorafenib in Huh7-R1 cells, indicating the importance of Akt in drug sensitivity. Sorafenib 64-73 AKT serine/threonine kinase 1 Homo sapiens 17-20 21205925-10 2011 In conclusion, activation of PI3K/Akt signaling pathway mediates acquired resistance to sorafenib in HCC, and the combination of sorafenib and MK-2206, an Akt inhibitor, overcomes the resistance at clinical achievable concentrations. Sorafenib 88-97 AKT serine/threonine kinase 1 Homo sapiens 34-37 21205925-10 2011 In conclusion, activation of PI3K/Akt signaling pathway mediates acquired resistance to sorafenib in HCC, and the combination of sorafenib and MK-2206, an Akt inhibitor, overcomes the resistance at clinical achievable concentrations. Sorafenib 129-138 AKT serine/threonine kinase 1 Homo sapiens 155-158 21187475-0 2010 PI-103 and sorafenib inhibit hepatocellular carcinoma cell proliferation by blocking Ras/Raf/MAPK and PI3K/AKT/mTOR pathways. Sorafenib 11-20 AKT serine/threonine kinase 1 Homo sapiens 107-110 21187475-7 2010 However, sorafenib as a single agent increased AKT(Ser473) and mTOR phosphorylation. Sorafenib 9-18 AKT serine/threonine kinase 1 Homo sapiens 47-50 21187475-12 2010 CONCLUSION: The combination of sorafenib and PI-103 can significantly inhibit EGF-stimulated Huh7 proliferation by blocking both Ras/Raf/MAPK and PI3K/AKT/mTOR pathways. Sorafenib 31-40 AKT serine/threonine kinase 1 Homo sapiens 151-154 20490331-0 2010 Sorafenib downregulates ERK/Akt and STAT3 survival pathways and induces apoptosis in a human neuroblastoma cell line. Sorafenib 0-9 AKT serine/threonine kinase 1 Homo sapiens 28-31 20810384-6 2010 Combined treatments of sorafenib with erlotinib or cetuximab produced combination index values between 0.02 and 0.5, suggesting a significant synergistic activity to inhibit soft agar colony formation in all cancer cell lines, which was accompanied by a marked blockade in mitogen-activated protein kinase and AKT signals. Sorafenib 23-32 AKT serine/threonine kinase 1 Homo sapiens 310-313 20950443-7 2010 Apoptosis and necrosis rates increased significantly with most pronounced effects after 96 h. Antiproliferative effects of Sorafenib were associated with a decreased phosphorylation of Akt (Ser473 and Thr308), FoxO3A (Thr32) and 4EBP-1 (Ser65 and Thr70) as early as 0.5 h after treatment. Sorafenib 123-132 AKT serine/threonine kinase 1 Homo sapiens 185-188 20490331-11 2010 Our results indicate that sorafenib significantly decreased cell viability and increased apoptosis in human neuroblastoma cell line in association with down-regulation of p-ERK1/2, p-Akt, p-STAT3 survival pathways. Sorafenib 26-35 AKT serine/threonine kinase 1 Homo sapiens 183-186 20371721-8 2010 Phosphorylation of AKT was also reduced by sorafenib. Sorafenib 43-52 AKT serine/threonine kinase 1 Homo sapiens 19-22 19913321-0 2010 Synergistic interactions between sorafenib and bortezomib in hepatocellular carcinoma involve PP2A-dependent Akt inactivation. Sorafenib 33-42 AKT serine/threonine kinase 1 Homo sapiens 109-112 19913321-5 2010 RESULTS: Pretreatment with sorafenib enhanced bortezomib-induced apoptotic cell death by restoring bortezomib"s ability to inactivate Akt in PLC/PRF/5 cells. Sorafenib 27-36 AKT serine/threonine kinase 1 Homo sapiens 134-137 19913321-6 2010 Knocking down Akt1 by RNA-interference overcame apoptotic resistance to bortezomib in PLC/PRF/5 cells and ectopic expression of active Akt in HCC cells abolished the bortezomib sensitizing effect of sorafenib, indicating Akt inactivation plays a key role in mediating the combinational effects. Sorafenib 199-208 AKT serine/threonine kinase 1 Homo sapiens 14-18 19913321-6 2010 Knocking down Akt1 by RNA-interference overcame apoptotic resistance to bortezomib in PLC/PRF/5 cells and ectopic expression of active Akt in HCC cells abolished the bortezomib sensitizing effect of sorafenib, indicating Akt inactivation plays a key role in mediating the combinational effects. Sorafenib 199-208 AKT serine/threonine kinase 1 Homo sapiens 14-17 19913321-6 2010 Knocking down Akt1 by RNA-interference overcame apoptotic resistance to bortezomib in PLC/PRF/5 cells and ectopic expression of active Akt in HCC cells abolished the bortezomib sensitizing effect of sorafenib, indicating Akt inactivation plays a key role in mediating the combinational effects. Sorafenib 199-208 AKT serine/threonine kinase 1 Homo sapiens 135-138 19913321-7 2010 Moreover, okadaic acid, a protein phosphatase 2A (PP2A) inhibitor, reversed down-regulation of phospho-Akt (P-Akt) expression induced by co-treatment with sorafenib and bortezomib, and 1, 9 di-deoxy-forskolin, a PP2A agonist, restored bortezomib"s effect on P-Akt and apoptosis. Sorafenib 155-164 AKT serine/threonine kinase 1 Homo sapiens 103-106 19913321-7 2010 Moreover, okadaic acid, a protein phosphatase 2A (PP2A) inhibitor, reversed down-regulation of phospho-Akt (P-Akt) expression induced by co-treatment with sorafenib and bortezomib, and 1, 9 di-deoxy-forskolin, a PP2A agonist, restored bortezomib"s effect on P-Akt and apoptosis. Sorafenib 155-164 AKT serine/threonine kinase 1 Homo sapiens 110-113 19913321-7 2010 Moreover, okadaic acid, a protein phosphatase 2A (PP2A) inhibitor, reversed down-regulation of phospho-Akt (P-Akt) expression induced by co-treatment with sorafenib and bortezomib, and 1, 9 di-deoxy-forskolin, a PP2A agonist, restored bortezomib"s effect on P-Akt and apoptosis. Sorafenib 155-164 AKT serine/threonine kinase 1 Homo sapiens 110-113 20502062-10 2010 Due to the beneficial effect of sorafenib in HCC and strong activation of EGFR, ERK1 and AKT1, our patient received sorafenib. Sorafenib 116-125 AKT serine/threonine kinase 1 Homo sapiens 89-93 19913321-10 2010 Finally, sorafenib plus bortezomib significantly suppressed PLC/PRF/5 xenograft tumor growth, down-regulated P-Akt expression, and up-regulated PP2A activity. Sorafenib 9-18 AKT serine/threonine kinase 1 Homo sapiens 111-114 19913321-11 2010 CONCLUSIONS: The combination of sorafenib and bortezomib shows synergy in HCC through PP2A-dependent Akt inactivation. Sorafenib 32-41 AKT serine/threonine kinase 1 Homo sapiens 101-104 20038816-5 2009 Treated cell lines demonstrated sorafenib-induced rapid dephosphorylation of AKT followed shortly by near complete dephosphorylation of the constitutively phosphorylated ERK1/2. Sorafenib 32-41 AKT serine/threonine kinase 1 Homo sapiens 77-80 21127754-4 2008 Sorafenib effectively induced growth arrest in rhabdomyosarcoma cells, which was concurrent with inhibition of Akt and Erk signaling. Sorafenib 0-9 AKT serine/threonine kinase 1 Homo sapiens 111-114 21127754-5 2008 Studies of ligand-induced phosphorylation of Erk and Akt in rhabdomyosarcoma cells showed that insulin-like growth factor-1 is a potent activator, which can be blocked by treatment with sorafenib. Sorafenib 186-195 AKT serine/threonine kinase 1 Homo sapiens 53-56 18593924-8 2008 The PDGFR and c-Raf inhibitor sorafenib (BAY 43-9006; Bayer Pharmaceuticals), currently approved for treatment of advanced renal cell cancer, inhibits both basal and PDGFRbeta-mediated ERK1/2 and AKT activity and decreases cell proliferation in human schwannoma cells, suggesting that this drug constitutes a promising tool to treat schwannomas. Sorafenib 30-39 AKT serine/threonine kinase 1 Homo sapiens 196-199 18765530-4 2008 Twenty-four hours after exposure, the activities of extracellular signal-regulated kinase 1/2, AKT, and nuclear factor-kappaB were only modestly modulated by sorafenib and vorinostat treatment. Sorafenib 158-167 AKT serine/threonine kinase 1 Homo sapiens 52-98 18593924-8 2008 The PDGFR and c-Raf inhibitor sorafenib (BAY 43-9006; Bayer Pharmaceuticals), currently approved for treatment of advanced renal cell cancer, inhibits both basal and PDGFRbeta-mediated ERK1/2 and AKT activity and decreases cell proliferation in human schwannoma cells, suggesting that this drug constitutes a promising tool to treat schwannomas. Sorafenib 41-52 AKT serine/threonine kinase 1 Homo sapiens 196-199 17388918-4 2007 METHODS: Using a panel of pharmacological inhibitors (BAY 43-9006, PD98059, U0126, wortmannin, LY294002) we inhibited the MAPK and AKT signalling pathways at different levels and evaluated the effects on growth, survival and invasion of melanoma cells in monolayer and organotypic skin culture. Sorafenib 54-65 AKT serine/threonine kinase 1 Homo sapiens 131-134 16959960-7 2006 In addition, the combination of sorafenib and rottlerin reduced or completely inhibited the phosphorylation of extracellular signal-regulated kinase and Akt and down-regulated cell cycle regulatory proteins such as cyclin-D1, cyclin-D3, cyclin-dependent kinase (cdk)4, and cdk6 in a dose- and time-dependent manner. Sorafenib 32-41 AKT serine/threonine kinase 1 Homo sapiens 153-156 16985072-0 2006 Cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib in vitro: induction of apoptosis through Akt and c-Jun NH2-terminal kinase pathways. Sorafenib 52-61 AKT serine/threonine kinase 1 Homo sapiens 143-146 16985072-7 2006 These findings show that sorafenib interacts synergistically with bortezomib to induce apoptosis in a broad spectrum of neoplastic cell lines and show an important role for the Akt and JNK pathways in mediating synergism. Sorafenib 25-34 AKT serine/threonine kinase 1 Homo sapiens 177-180