Research Of Growth Inhibition And Mechanism By Berberine In Human Ovarian Cancer Cell In Vitro

Objective To investigate the effect of berberine on inhibition of proliferation through induction of apoptosis and the demethylation on mismatch repair gene hMLH1in human ovarian cancer SKOV3cells.Methods The inhibitory effect of berberine on the proliferation of human ovarian cancer SKOV3cells was evaluated by the MTT assay;after being treated with different dose of berberine, the cell cycle distribution and the apoptosis rate were analyed by flow cytometry (FCM); the changes of morphology and ultrastructure were observed by inverted microscopean and transmission electron microscope;the change of methylation status of CpG island in hMLH1gene promoter region was analyzed by MSP and the change of expression of bcl-2,bax,survivin and hMLHl mRNA was detected by real-time fluorescence quantitative RT-PCR in SKOV3cell.Results Berberine significantly inhibited the proliferation of human ovarian cancer SKOV3cells in a dose-dependent and time-dependentmanner, IC50of cisplatin dropped obviously when combined with berberine, the differences were significant among different groups (P<0.05); After treated with berberine, the increase of SKOV3cells in G0/G1phase and apoptosis rate were detected. SKOV3cells showed typical morphology and ultrastructure chatacter of apoptosis cell after treated with berberine.The CpG island in hMLHl gene promoter region in SKOV3cells showed hemimethylation, after being treated with berberine, methylation specificity strip of CpG island in hMLHl gene promoter bate and unmethylation specificity strip enhanced.Berberine obviously decrease the expression of bcl-2and survivin but increase the expression of bax and hMLH1mRNA.Conclusion:Berberine can inhibit proliferation of human ovarian cancer SKOV3cells through induction of apoptosis and demethylation effect on hMLH1gene, berberine can augment the chemotheraphy when combined with cisplatin.