Study On The Growth Inhibition And Apoptosis Induced By A Novel Benzoxazole Derivative In Human Hepatocarcinoma Cells

Objective: To investigate the anti-tumor activity and apoptosis induction effects of a novel benzoxazole derivative on human hepatocellular carcinoma cell,and explore the underlying molecular mechanisms.This experimental study aims to explore the inhibitory effect of a novel benzoxazole compound on liver cancer by using hepatocellular carcinoma cell line SMMC-7721 and HepG2 cells as the main research object,which may provide the theoretical foundation for studying the antitumor compound.Methods: The growth inhibitory effects of the novel benzoxazole derivative on human cancer cells were evaluated by CCK-8 assay.The apoptosis in hepatocellular carcinoma cell cells was analyzed by Hoechst 33258 staining,DNA ladder analyses,Annexin V-FITC/PI double-labeled flow cytometry analysis,and TUNEL methods.Western blotting was performed to detect the expression of the apoptosis-related proteins,including caspase-3,caspase-9,bcl-2,Bax and PARP in SMMC-7721 and HepG2 cells.Furthermore,hepatocellular carcinoma cells-bearing nude mice model were established to evaluate the antitumour effect of novel benzoxazole derivative on liver cancer cells in vivo.Results: The novel benzoxazole derivative displayed an obviously strong inhibitory effect on human cancer cell lines including SGC7901,ACHN,SMMC-7721,A549 and HT-29 cells.The hepatocellular carcinoma SMMC-7721 and HepG2 cellular proliferative activity in novel benzoxazole derivative treatment group was much lower than that of control group(P < 0.05).Hoechst 33258 staining,DNA ladder analyses,Annexin V-FITC/PI double-labeled flow cytometry analysis,and TUNEL methods demonstrated that the novel benzoxazole derivativel induced SMMC-7721 cells and HepG2 cells apoptosis.The cell apoptosis rate in novel benzoxazole derivative treatment group was significantly higher than that in the control group(P < 0.05).The novel benzoxazole derivative activated the caspases-3,caspases-9 and PARP,and down-regulated the expression of bcl-2 in hepatocellular carcinoma cells(P < 0.05)and up-regulated the expression of Bax(P < 0.05),thus inducing apoptosis.In vivo,the novel benzoxazole derivative delayed the tumor growth of hepatocellular carcinoma cells in nude mice models.Conclusions: The novel benzoxazole derivative inhibited the proliferation of hepatocellular carcinoma cell through inducing its apoptosis by cleaving of caspases-3,caspases-9 and PARP,as well as down-regulating the expression of bcl-2 and up-regulating the expression of Bax in hepatocellular carcinoma cells.This effect displays a trend of concentration-dependent increase.In addition,The novel benzoxazole derivative can delay the tumor growth of hepatocellular carcinoma cells in vivo.