An experimental study on ursodeoxycholic acid-selectively induced apoptosis and proliferative inhibition on human hepatoma cell lines

AIM: To investigate the effect of inducing apoptosis and proliferative inhibition on hepatoma cell lines by ursodeoxycholic acid (UDCA), and its mechanisms. METHODS: UDCA effects on cell proliferation, apoptosis, cell cycle and the expression of Bax/bcl-2 genes for two human hepatoma cell lines HepG2 and BEL7402, and normal human hepatic cell line L-02 in vitro were detected by applying MTT assay, flow cytometry, TUNEL (terminal deoxynucleotidyl transferase mediated nick end labeling) assay, Wright-Giemsa staining, electron microscopy and immunocytochemistry. RESULTS: UDCA could strongly inhibit the proliferation of HepG2 and BEL7402 cell lines, and with the concentration of UDCA increasing, the effect of proliferative inhibition would become more obvious(r 2=0.96, P0.01;r 2=0.97, P0.01;48 h). The IC 50 responses to HepG2 and BEL7402 were 0.92 mmol·L -1 , 0.86 mmol·L -1 , respectively. The apoptosis rates (UDCA 1.0 mmol·L -1 ) of HepG2 and BEL7402 were (42±6) % and (44± 4) %, respectively with higher significance than that of L-02 (P0.01). UDCA could arrest cell cycle to S phase. Treated HepG2 with UDCA(0.8 mmol·L -1 ), the expression of bcl-2 decreased from (24.3± 2.4) % to (10.1±1.6) % and the expression of Bax increased from (43±5) % to (59±3) %(P 0.01), while treated BEL7402, the expression of bcl-2 decreased from (21.6±1.8) % to (11.6± 2.1) %, the expression of Bax increased from (44±4) % to (59±3) %(P0.01).UDCA had no obvious effect on L-02 cell line. CONCLUSION: UDCA may be selectively inhibit proliferation and induce apoptosis of HepG2 and BEL7402 cell lines by blocking cell cycle and regulating the expression of Bax/bcl-2 genes.