Effect of 5-fluorouracil combined with mifepristone on cell proliferation of human cervical cancer cell line SiHa and its mechanism

Objective: To investigate the inhibitory effect of 5-fluorouracil (5-Fu) combined with mifepristone (MIF) on the cell proliferation of human cervical cancer cell line SiHa in vitro, and to explore the possible mechanism. Methods: SiHa cells were cultured in vitro. The proliferation inhibitory rates of SiHa cells treated with different concentrations of MIF or 5-Fu alone and the combination of MIF and 5-Fu were detected by MTT assay. The changes of apoptosis rate and the cell cycle of SiHa cells were determined by flow cytometry. The expression levels of p53, Bcl-2 and Bax proteins in SiHa cells were examined by Western blotting.  Results: Different concentrations of MIF or 5-Fu could inhibit the proliferation of SiHa cells in a dose- and time-dependent manner (P＜0.05). 5-Fu in combination with different concentrations of MIF could significantly enhance this inhibitory effect (P＜0.05) in a dose-dependent manner. The expression levels of p53 and Bax proteins were increased while the expression level of Bcl-2 protein was decreased in SiHa cells after treatment with 5-Fu plus MIF, and these effects were in a dose-dependent manner.  Conclusion: MIF can enhance the inhibitory effect of 5-Fu on SiHa cells, and promote the apoptosis of SiHa cells induced by 5-Fu. The mechanism may be associated with the down-regulation of Bcl-2 protein and up-regulation of p53 and Bax proteins. DOI:10.3781/j.issn.1000-7431.2011.08.008