瑞戈非尼联合哌立福辛诱导人肝癌HepG2细胞凋亡的分子机制研究

doi:10.11904/j.issn.1002-3070.2021.05.004

Abstract

Abstract: Objective The Objective of this study was to investigate the molecular mechanism of regorafenib combined with perifoxin(AKT inhibitor)in apoptosis induction of human hepatoma HepG2 cells. Methods After treated with different concentrations of regorafenib(1,5,10,15,20 and 25 μmol/L),the cell survival rate was detected in hepatoma cells by CCK-8 assay;and then different concentrations of regorafenib(0,5,10 and 20 μmol/L)were setup.Flow cytometry was used to detect apoptosis.The expression of Bax,Bcl-2,P-AKT,AKT,p21,p27,Cleaved-caspase-8 and Cleaved-caspase-9 was detected by Western blot.Perifosine group(10 μmol/L),regorafenib group(20 μmol/L)and the drug combination group(perifosine 10 μmol/L combined with regorafenib 20 μmol/L)were set to detect cell apoptosis and related protein expression changes. Results Regorafenib inhibited proliferation of hepatoma cells in a dose-dependent manner from the concentration of 5 μmol/L(P＜0.05).The expression of Bcl-2 and P-AKT was down-regulated and the expression of Bax,p21,p27,Cleaved-caspase-8 and Cleaved-caspase-9 was up-regulated(P＜0.05).After the combined application of regorafenib and perifosine,the apoptosis rate and Bax expression were significantly increased(P＜0.05),and the decrease of Bcl-2 and P-AKT expression was more obvious than that of perifosine or regorafenib alone(P＜0.05). Conclusion Regorafenib can induce apoptosis in hepatma cells by increasing the expression of p21,p27,Bax,Caspase-8 and Caspase-9,and reducing the expression of Bcl-2 and P-AKT.The combined application of regorafenib and perifosine significantly increases the apoptosis rate of hepatma cells,providing a new theoretical basis and ideas for the drug treatment of liver cancer.

Key words: Regorafenib, AKT inhibitor, Hepatoma carcinoma, Apoptosis

CLC Number:

R735.7

CHEN Xuejian, WANG Wei, ZHOU Jian, LI Ning, ZHANG Haopeng, XU Lishan. Research on the molecular mechanism of regorafenib combined with perifosine in inducing apoptosis of human hepatoma HepG2 cells[J]. Journal of Practical Oncology, 2021, 35(5): 408-413.

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URL: http://journal09.magtechjournal.com/Jwk3_syzlxzz/EN/10.11904/j.issn.1002-3070.2021.05.004

http://journal09.magtechjournal.com/Jwk3_syzlxzz/EN/Y2021/V35/I5/408

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Research on the molecular mechanism of regorafenib combined with perifosine in inducing apoptosis of human hepatoma HepG2 cells

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