PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 23533466-6 2013 Our studies showed that bufalin could reverse resistance to reversible and irreversible EGFR-TKIs induced by exogenous HGF in EGFR mutant lung cancer cells by inhibiting the Met/PI3K/Akt pathway and inducing death signaling. bufalin 24-31 AKT serine/threonine kinase 1 Homo sapiens 183-186 24581171-10 2014 Certain changes of expression of AKT/GSK3beta/beta-catenin/E-cadherin signaling pathway-related proteins were in tumor tissues, which were related to the bufalin dose. bufalin 154-161 AKT serine/threonine kinase 1 Homo sapiens 33-36 24581171-13 2014 Inhibition of AKT/GSK3beta/beta-catenin/E-cadherin signaling pathways by bufalin may show therapeutic effects in advanced HCC patients. bufalin 73-80 AKT serine/threonine kinase 1 Homo sapiens 14-17 23533466-0 2013 Bufalin Reverses HGF-Induced Resistance to EGFR-TKIs in EGFR Mutant Lung Cancer Cells via Blockage of Met/PI3k/Akt Pathway and Induction of Apoptosis. bufalin 0-7 AKT serine/threonine kinase 1 Homo sapiens 111-114 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. bufalin 142-149 AKT serine/threonine kinase 1 Homo sapiens 75-78 23799775-4 2013 It was found that bufalin rapidly elicited activation of the ClC-3 Cl(-) channel and subsequently induced apoptosis through inhibition of the PI3K/Akt/mTOR pathway. bufalin 18-25 AKT serine/threonine kinase 1 Homo sapiens 147-150 23870199-3 2013 In the present study, we investigated the effect of bufalin on the inhibition of an AKT-related signaling pathway, and examined the relationship between regulatory proteins and anti-tumor effects in hepatoma cells. bufalin 52-59 AKT serine/threonine kinase 1 Homo sapiens 84-87 23870199-9 2013 CONCLUSIONS: Bufalin is a potential anti-HCC therapeutic candidate through its inhibition of the AKT/GSK3beta/beta-catenin/E-cadherin signaling pathway. bufalin 13-20 AKT serine/threonine kinase 1 Homo sapiens 97-100 22922805-0 2012 AKT serine/threonine protein kinase modulates bufalin-triggered intrinsic pathway of apoptosis in CAL 27 human oral cancer cells. bufalin 46-53 AKT serine/threonine kinase 1 Homo sapiens 0-3 22858649-0 2012 Bufalin increases sensitivity to AKT/mTOR-induced autophagic cell death in SK-HEP-1 human hepatocellular carcinoma cells. bufalin 0-7 AKT serine/threonine kinase 1 Homo sapiens 33-36 22922805-8 2012 In contrast, CAL 27 cells overexpressing constitutively active AKT (CAL 27/CA-AKT) were exposed to bufalin at different concentrations, and cell growth remained unchanged. bufalin 123-130 AKT serine/threonine kinase 1 Homo sapiens 90-93 22922805-9 2012 Bufalin exhibited minimal apoptotic effects on CAL 27/CA-AKT cells. bufalin 0-7 AKT serine/threonine kinase 1 Homo sapiens 69-72 22922805-10 2012 Taken together, bufalin induced G0/G1 phase arrest and provoked the intrinsic apoptotic pathway via AKT activation in CAL 27 cells. bufalin 16-23 AKT serine/threonine kinase 1 Homo sapiens 112-115 22922805-8 2012 In contrast, CAL 27 cells overexpressing constitutively active AKT (CAL 27/CA-AKT) were exposed to bufalin at different concentrations, and cell growth remained unchanged. bufalin 123-130 AKT serine/threonine kinase 1 Homo sapiens 75-78 22285700-10 2012 Based on our results, bufalin induces apoptotic cell death in T24 cells through suppressing AKT activity and anti-apoptotic Bcl-2 protein as well as inducing pro-apoptotic Bax protein. bufalin 22-29 AKT serine/threonine kinase 1 Homo sapiens 92-95 22408435-0 2012 Bufalin induces lung cancer cell apoptosis via the inhibition of PI3K/Akt pathway. bufalin 0-7 AKT serine/threonine kinase 1 Homo sapiens 70-73 21617941-5 2012 Furthermore, the inhibitory effect of bufalin on pERK was blocked by the PI3kinase inhibitor LY294002, suggesting that the reduction in pERK induced by bufalin might be mediated by AKT in these two HCC cell lines. bufalin 38-45 AKT serine/threonine kinase 1 Homo sapiens 181-184 21617941-5 2012 Furthermore, the inhibitory effect of bufalin on pERK was blocked by the PI3kinase inhibitor LY294002, suggesting that the reduction in pERK induced by bufalin might be mediated by AKT in these two HCC cell lines. bufalin 152-159 AKT serine/threonine kinase 1 Homo sapiens 181-184 22408435-5 2012 In addition, A549 cells were treated by Akt inhibitor LY294002 in combination with bufalin and the activation of Akt and Caspase-3 as well as the expression levels of Bax, Bcl-2 and livin were examined by Western blot analysis. bufalin 83-90 AKT serine/threonine kinase 1 Homo sapiens 40-43 22408435-7 2012 Mechanistically, we found that bufalin inhibited the activation of Akt. bufalin 31-38 AKT serine/threonine kinase 1 Homo sapiens 67-70 22408435-8 2012 Moreover, bufalin synergized with Akt inhibitor to induce the apoptosis of A549 cells and this was associated with the upregulation of Bax expression, the downregulation of Bcl-2 and livin expression, and the activation of Caspase-3. bufalin 10-17 AKT serine/threonine kinase 1 Homo sapiens 34-37 22408435-9 2012 In conclusion, our findings demonstrate that bufalin induces lung cancer cell apoptosis via the inhibition of PI3K/Akt pathway and suggest that bufalin is a potential regimen for combined chemotherapy to overcome the resistance of lung cancer cells to chemotherapeutics induced apoptosis. bufalin 45-52 AKT serine/threonine kinase 1 Homo sapiens 115-118 35126601-4 2022 Furthermore, in vitro cell experiments were used to verify bufalin activation of AKT and MAPK signaling pathways in human mesangial cells. bufalin 59-66 AKT serine/threonine kinase 1 Homo sapiens 81-84 34512368-3 2021 In this review, we focus on summarizing some representative natural active compounds, mainly including curcumin, resveratrol, paclitaxel, Bufalin, and Ursolic acid that may ultimately trigger cancer cell death through the regulation of some key autophagic signaling pathways, such as RAS-RAF-MEK-ERK, PI3K-AKT-mTOR, AMPK, ULK1, Beclin-1, Atg5 and p53. bufalin 138-145 AKT serine/threonine kinase 1 Homo sapiens 306-309 21181095-5 2011 Furthermore, we show that bufalin increased the phosphorylation of Akt and ERK1/2 while inhibited FoxO3a expression. bufalin 26-33 AKT serine/threonine kinase 1 Homo sapiens 67-70 20963488-10 2010 Furthermore, bufalin inhibited the protein expressions and phosphorylation of Akt, NF-kappaB, p44/42 MAPK (ERK1/2) and p38 MAPK in A549 cells. bufalin 13-20 AKT serine/threonine kinase 1 Homo sapiens 78-81 20963488-11 2010 Our results suggest that bufalin inhibits the human lung cancer cell proliferation via VEGFR1/VEGFR2/EGFR/c-Met-Akt/p44/42/p38-NF-kappaB signaling pathways; bufalin may have a wide therapeutic and/or adjuvant therapeutic application in the treatment of human NSCLC. bufalin 25-32 AKT serine/threonine kinase 1 Homo sapiens 112-115 19343001-0 2009 PI3K/Akt is involved in bufalin-induced apoptosis in gastric cancer cells. bufalin 24-31 AKT serine/threonine kinase 1 Homo sapiens 5-8 19343001-6 2009 It should be noted that bufalin transiently activated the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway and then inhibited it completely, and upregulated the Casitas B-lineage lymphoma (Cbl) family of ubiquitin ligases, upstream modulators of PI3K. bufalin 24-31 AKT serine/threonine kinase 1 Homo sapiens 95-98 19343001-8 2009 These results suggested that the PI3K/Akt pathway might play a key role in bufalin-induced apoptosis in gastric cancer MGC803 cells. bufalin 75-82 AKT serine/threonine kinase 1 Homo sapiens 38-41 34935692-8 2021 Bufalin inhibited phosphorylation of EGFR, protein kinase B (AKT), and extracellular signal-regulated kinase (ERK). bufalin 0-7 AKT serine/threonine kinase 1 Homo sapiens 61-64 34935692-9 2021 CONCLUSION: Bufalin suppresses the proliferation of ovarian cancer cells through the EGFR/AKT/ERK signaling pathway. bufalin 12-19 AKT serine/threonine kinase 1 Homo sapiens 90-93 33148004-14 2020 Bufalin could inhibit the proliferation, invasion, and metastasis of cancer cells through multiple signaling pathways, such as PI3K/AKT, Hedgehog, MAPK/JNK, Wnt/[Formula: see text]-catenin, TGF-[Formula: see text]/Smad, Integrin signaling pathway, and NF-KB signaling pathway via KEGG analysis. bufalin 0-7 AKT serine/threonine kinase 1 Homo sapiens 132-135 33530915-0 2021 Effect of PI3K/AKT/mTOR Signaling Pathway on Regulating and Controlling the Anti-Invasion and Metastasis of Hepatoma Cells by Bufalin. bufalin 126-133 AKT serine/threonine kinase 1 Homo sapiens 15-18 33530915-2 2021 OBJECTIVE: In this study, we explored the effect of PI3K/AKT/mTOR autophagy related signaling pathway on regulating and controlling the invasion and metastasis of liver cancer cells by Bufalin. bufalin 185-192 AKT serine/threonine kinase 1 Homo sapiens 57-60 32231716-7 2020 Western blot assay showed that Bufalin inhibited MEK/ERK and PI3-K/AKT signaling pathways by inhibiting the expression of p-c-Met, which in turn affected the expression of apoptosis-related protein Mcl-1, and the invasion-associated proteins E-cadherin, MMP9 and Snail. bufalin 31-38 AKT serine/threonine kinase 1 Homo sapiens 67-70 30468278-10 2019 Therefore, our data provide evidence that bufalin induces autophagy in MGC803 cells via both Akt/mTOR/p70S6K and ERK signaling pathways, and Cbl-b-mediated suppression of mTOR and activation of ERK1/2 might play an important role. bufalin 42-49 AKT serine/threonine kinase 1 Homo sapiens 93-96 30128000-0 2018 Bufalin suppresses the proliferation and metastasis of renal cell carcinoma by inhibiting the PI3K/Akt/mTOR signaling pathway. bufalin 0-7 AKT serine/threonine kinase 1 Homo sapiens 99-102 30128000-4 2018 Further mechanistic study revealed that bufalin reduced the expression of phosphorylated (phospho)-Akt and phospho-mammalian target of rapamycin (mTOR). bufalin 40-47 AKT serine/threonine kinase 1 Homo sapiens 99-102 30128000-6 2018 Thus, the present results suggest that bufalin induces cell cycle arrest and suppresses metastasis; this process may be associated with the PI3K/Akt/mTOR signaling pathway. bufalin 39-46 AKT serine/threonine kinase 1 Homo sapiens 145-148 29568394-8 2018 Taken together, cardiac glycoside bufalin induces mitotic entry delay and mitotic arrest in cancer cells through inhibition of Aurora A/B activation via PI3K-Akt pathway. bufalin 34-41 AKT serine/threonine kinase 1 Homo sapiens 158-161 29622868-0 2018 Bufalin Enhances the Cytotoxity of Human Multiple Myeloma Cells H929 to AKT Inhibitor MK2206: The Role of Protein AKT Phosphorylation. bufalin 0-7 AKT serine/threonine kinase 1 Homo sapiens 72-75 29622868-0 2018 Bufalin Enhances the Cytotoxity of Human Multiple Myeloma Cells H929 to AKT Inhibitor MK2206: The Role of Protein AKT Phosphorylation. bufalin 0-7 AKT serine/threonine kinase 1 Homo sapiens 114-117 28492559-0 2017 MK2206 enhances the cytocidal effects of bufalin in multiple myeloma by inhibiting the AKT/mTOR pathway. bufalin 41-48 AKT serine/threonine kinase 1 Homo sapiens 87-90 28492559-3 2017 Previous studies conducted by our group demonstrated that bufalin activated the AKT/mTOR pathway in myeloma cells, which is considered an essential pathway to disease progression and is related to drug resistance in MM. bufalin 58-65 AKT serine/threonine kinase 1 Homo sapiens 80-83 28492559-4 2017 In view of the significant role of AKT in MM, the allosteric AKT inhibitor MK2206 was selected in order to enhance the antitumor effects of bufalin in different MM cell lines (NCI-H929, U266, LP-1 and RPMI8226). bufalin 140-147 AKT serine/threonine kinase 1 Homo sapiens 61-64 28492559-11 2017 In conclusion, the data suggested that MK2206 significantly enhanced the cytocidal effects of bufalin in MM cells, regardless of the sensitivity to bortezomib, via the inhibition of the AKT/mTOR pathway. bufalin 94-101 AKT serine/threonine kinase 1 Homo sapiens 186-189 27507851-8 2016 Also, the effects of BF on PI3K/AKT/GSK3beta and apoptosis signal cascades were enhanced in APOE knockdown cells. bufalin 21-23 AKT serine/threonine kinase 1 Homo sapiens 32-35 27425252-7 2016 The combination of bufalin and SAHA was particular efficient in attenuating AKT activation and reducing Bcl-2 levels. bufalin 19-26 AKT serine/threonine kinase 1 Homo sapiens 76-79 27357249-0 2016 Bufalin reverses intrinsic and acquired drug resistance to cisplatin through the AKT signaling pathway in gastric cancer cells. bufalin 0-7 AKT serine/threonine kinase 1 Homo sapiens 81-84 27357249-2 2016 Bufalin, a traditional Chinese medicine, shows significant anticancer activity by inhibiting the AKT pathway. bufalin 0-7 AKT serine/threonine kinase 1 Homo sapiens 97-100 27357249-6 2016 It was demonstrated that bufalin synergized with cisplatin to inhibit proliferation and promote apoptosis of GC cells by diminishing the activation of cisplatin-induced AKT under normoxic and hypoxic conditions. bufalin 25-32 AKT serine/threonine kinase 1 Homo sapiens 169-172 27357249-7 2016 Bufalin also inhibits cisplatin-activated molecules downstream of AKT that affect proliferation and apoptosis, including glycogen synthase kinase, mammalian target of rapamycin, ribosomal protein S6 Kinase and eukaryotic translation initiation factor-4E-binding protein-1. bufalin 0-7 AKT serine/threonine kinase 1 Homo sapiens 66-69 26782953-0 2016 Bufalin enhances anti-angiogenic effect of sorafenib via AKT/VEGF signaling. bufalin 0-7 AKT serine/threonine kinase 1 Homo sapiens 57-60 26662961-4 2016 Our results showed that arenobufagin and bufalin could significantly inhibit the proliferation and survival of HER2 overexpressing breast cancer cells, along with the declination of SRC-1, SRC-3, nuclear transcription factor E2F1, phosphorylated AKT, and ERK. bufalin 41-48 AKT serine/threonine kinase 1 Homo sapiens 246-249 26958938-0 2016 Bufalin suppresses hepatocellular carcinoma invasion and metastasis by targeting HIF-1alpha via the PI3K/AKT/mTOR pathway. bufalin 0-7 AKT serine/threonine kinase 1 Homo sapiens 105-108 26958938-11 2016 Taken together, our results suggest that bufalin suppresses hepatic tumor invasion and metastasis and that this process may be related to the PI3K/AKT/mTOR/ HIF-1alpha axis. bufalin 41-48 AKT serine/threonine kinase 1 Homo sapiens 147-150 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. bufalin 66-73 AKT serine/threonine kinase 1 Homo sapiens 141-144 26770191-11 2015 In the Bufalin-treated cultured cells and/or xenograft tumors, the expressions of PTEN, Bad, Bax, and Caspase-3 were significantly increased, while p-AKT and Bcl-xL significantly decreased. bufalin 7-14 AKT serine/threonine kinase 1 Homo sapiens 150-153 26758421-4 2016 Mechanistic study reveals that Bufalin suppresses the integrin alpha2/FAK/AKT1/ GSK3beta signaling. bufalin 31-38 AKT serine/threonine kinase 1 Homo sapiens 74-78 26381511-0 2015 Bufalin Reverses Resistance to Sorafenib by Inhibiting Akt Activation in Hepatocellular Carcinoma: The Role of Endoplasmic Reticulum Stress. bufalin 0-7 AKT serine/threonine kinase 1 Homo sapiens 55-58 26381511-3 2015 Bufalin is the major active ingredient of the traditional Chinese medicine Chan su, which inhibits Akt activation; therefore, Chan su is currently used in the clinic to treat cancer. bufalin 0-7 AKT serine/threonine kinase 1 Homo sapiens 99-102 26381511-8 2015 Silencing IRE1 with siRNA blocked the bufalin-induced Akt inactivation, but silencing eukaryotic initiation factor 2 (eIF2) or C/EBP-homologous protein (CHOP) did not have the same effect. bufalin 38-45 AKT serine/threonine kinase 1 Homo sapiens 54-57 26381511-11 2015 Thus, Bufalin reversed acquired resistance to sorafenib by downregulating phosphorylated Akt in an ER-stress-dependent manner via the IRE1 pathway. bufalin 6-13 AKT serine/threonine kinase 1 Homo sapiens 89-92 26463323-10 2015 The results of Western blot analysis showed that the expression of p-EGFR, p-cMet, p-AKT, p-ERK, vimentin and snail in H1975AR cells treated with bufalin puls afatinb was down-regulated markedly, and the expression of E-cadherin was up-regulated markedly. bufalin 146-153 AKT serine/threonine kinase 1 Homo sapiens 85-88 26463323-12 2015 The possible mechanism of combined treatment with bufalin and afatinib may be related to the blocking of cMet/PI3K/AKT and cMet/MAPK/ERK pathways and inhibiting of epithelial-mesenchymal transition. bufalin 50-57 AKT serine/threonine kinase 1 Homo sapiens 115-118 23949904-8 2015 Bufalin attenuated phosphoinisitide-3-kinase (PI3K) and phosphorylation of AKT which was associated with reduced levels of nuclear factor kappa B (NF-kappaB). bufalin 0-7 AKT serine/threonine kinase 1 Homo sapiens 75-78 23949904-10 2015 Based on these observations, we propose that bufalin is acts as an antiinvasive agent by inhibiting MMP-2 and -9 and involving PI3K/AKT and NF-kappaB pathways. bufalin 45-52 AKT serine/threonine kinase 1 Homo sapiens 132-135