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Effect of Akt inhibitor MK-2206 on the biological behavior of hepatoma cell huh7 and its mechanism |
XIONG Lin HE Xiaoqin FAN Li XU Ximing |
Cancer Center, Renmin Hospital of Wuhan University, Hubei Province, Wuhan 430060, China |
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Abstract Objective To investigate the effect of MK-2206 on the growth of hepatoma cells huh7 and its mechanism of action. Methods Human hepatoma cell line huh7 was cultured in vitro, and huh7 cells were treated with different concentrations (0, 2.5, 5, 10, 20, 40 μmol/L) MK-2206. Cell proliferation was detected by CCK-8; apoptosis was detected by flow cytometry; protein expression was detected by Western blot. Results Compared with the control group (0 μmol/L), MK-2206 significantly inhibited the proliferation of hepatoma cell line huh7 in a dose-and time-dependent manner. MK-2206 had the tendency to reduce the migration ability of huh7, but there was no statistically significant difference. MK-2206 induced apoptosis of huh7 cells (P < 0.05) and significantly inhibited Akt protein expression (P < 0.05). Conclusion The Akt inhibitor MK-2206 can regulates the biological behavior of hepatoma cell huh7 by regulating the PI3K/Akt signaling pathway.
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[1] Forner A,Llovet JM,Bruix J. Hepatocellular carcinoma [J]. Lancet,2012,379(9822):1245-1255.
[2] Zhu RX,Seto WK,Lai CL,et al. Epidemiology of Hepatocellular Carcinoma in the Asia-Pacific Region [J]. Gut Liver,2016,10(3):332-339.
[3] Cha C. Surgical therapy for hepatocellular carcinoma:formulating a rational approach [J]. J Clin Gastroenterol,2013, 47 Suppl:S30-S36.
[4] Forner A,Gilabert M,Bruix J,et al. Treatment of intermediate-stage hepatocellular carcinoma [J]. Nat Rev Clin Oncol,2014,11(9):525-535.
[5] Mazzaferro V. Sorafenib in advanced hepatocellular carcinoma [J]. N Engl J Med,2008,359(23):378-390.
[6] Cheng AL,Kang YK,Chen Z,et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma:a phase Ⅲ randomised,double-blind,placebo-controlled trial [J]. Lancet Oncology,2009,10(1):4-5.
[7] Wang FZ,Peng-Jiao,Yang NN,et al. PF-04691502 triggers cell cycle arrest,apoptosis and inhibits the angiogenesis in hepatocellular carcinoma cells [J]. Toxicol Lett,2013,220(2):150-156.
[8] Agarwal E,Chaudhuri A,Leiphrakpam PD,et al. Akt inhibitor MK-2206 promotes anti-tumor activity and cell death by modulation of AIF and Ezrin in colorectal cancer [J]. BMC Cancer,2014,14:145.
[9] Ma CX,Suman V,Goetz MP,et al. A Phase Ⅱ trial of neoadjuvant MK2206,an AKT inhibitor,with anastrozole in clinical stage 2 or 3 PIK3CA mutant ER positive and HER2 negative breast cancer [J]. Clinical Cancer Res,2017, 23(22):6823-6832.
[10] Llovet JM,Villanueva A,Lachenmayer A,et al. Advances in targeted therapies for hepatocellular carcinoma in the genomic era [J]. Nat Rev Clin Oncol,2015,12(7):408-424.
[11] Zhang CZ,Wang XD,Wang HW,et al. Sorafenib inhibits liver cancer growth by decreasing mTOR,AKT,and PI3K expression [J]. J BUON,2015,20(1):218-222.
[12] Li YC,He SM,He ZX,et al. Plumbagin induces apoptotic and autophagic cell death through inhibition of the PI3K/Akt/mTOR pathway in human non-small cell lung cancer cells [J]. Cancer Lett,2014,344(2):239-259.
[13] Yang J,Pi C,Wang G. Inhibition of PI3K/Akt/mTOR pathway by apigenin induces apoptosis and autophagy in hepatocellular carcinoma cells [J]. Biomed Pharmacother,2018, 103:699-707.
[14] Lu JW,Lin YM,Lai YL,et al. MK-2206 induces apoptosis of AML cells and enhances the cytotoxicity of cytarabine [J]. Med Oncol,2015,32(7):206.
[15] Ji D,Zhang Z,Cheng L,et al. The combination of RAD001 and MK-2206 exerts synergistic cytotoxic effects against PTEN mutant gastric cancer cells:involvement of MAPK-dependent autophagic,but not apoptotic cell death pathway [J]. PLoS One,2014,9(1):e85 116.
[16] Malkomes P,Lunger I,Luetticke A,et al. Selective AKT inhibition by MK-2206 represses colorectal cancer-initiating stem cells [J]. Ann Surg Oncol,2016,23(9):2849-2857.
[17] Gupta S,Argiles G,Munster PN,et al. A phase Ⅰ trial of combined ridaforolimus and MK-2206 in patients with advanced malignancies [J]. Clin Cancer Res,2015,21(23):5235-5244.
[18] Hu C,Dadon T,Chenna V,et al. Combined inhibition of cyclin-dependent kinases (Dinaciclib)and AKT(MK-2206)blocks pancreatic tumor growth and metastases in patient-derived xenograft models [J]. Mol Cancer Ther,2015,14(7):1532-1539.
[19] Ramanathan RK,Mcdonough SL,Kennecke HF,et al. Phase 2 study of MK-2206,an allosteric inhibitor of AKT,as second-line therapy for advanced gastric and gastroesophageal junction cancer:A SWOG cooperative group trial(S1005)[J]. Cancer,2015,121(13):2193-2197. |
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