Chenodeoxycholic acid derivative HS-1200 can effectively inhibit the growth of liver tumor cell line BEL7402, its role with the drug concentration and prolonged the role of time to enhance, showing a certain dose, time-dependent;chenodeoxycholic acid derivatives HS -1200 inhibited the growth of human hepatoma cell line BEL7402. The growth inhibition was related to HS-1200-induced apoptosis of liver tumor cells. HS-1200 had no effect on growth inhibition and apoptosis induction in normal liver cell lines. The mechanism of HS-1200-induced apoptosis may be that HS-1200 up-regulates Bax and reduces the expression of Bcl-2, thereby increasing the permeability of mitochondrial membrane, releasing cytochrome C from the mitochondria into the cytoplasm, activating caspase-9, activating caspase-3 cleaves caspase-3 to induce apoptosis, but caspase-8-specific inhibitors did not alter HS-1200-induced apoptosis during apoptosis, and HS-1200 induced liver tumor cells. The apoptotic pathway is an endogenous apoptotic pathway.
To investigate the effect and mechanism of chenodeoxycholic acid derivative HS-1200 on apoptosis and inhibition of proliferation of hepatoma cell line. Methods: 40, 60 and 80p-M HS-1200 were used in the liver tumor cell line BEL7402. Cell viability was detected by MTT at 12, 24 and 36 hours after action. Flow cytometry, DNA ladder and fluorescence microscopy. The expression of bcl-2, bax, cytochrome C and caspase-3 were detected by Western-blot. The results showed that HS-1200 could effectively inhibit the growth of BEL7402, and its effect was enhanced with the increase of drug concentration and the duration of action. The results showed that the apoptotic rate increased significantly with the concentration and duration of action (P <0.05). Ho-echst33258 staining showed that the apoptotic morphological changes were observed. Gel electrophoresis showed typical apoptotic trapezoidal bands. Western blot results showed that HS-1200 could enhance bax, Cytochrome C and caspase-3 expression, and decreased the expression of bcl-2 protein. Conclusion: HS-1200 can significantly inhibit the proliferation and induce apoptosis of BEL7402. The mechanism may be to enhance the expression of bax, cytochrome c and caspase-3 and decrease the expression of bcl-2. HS-1200 may be an effective of the treatment of liver cancer chemotherapy drugs.