Mifepristone sensitizing cisplatin for cervical adenocarcinoma HeLa cell sensitivity to chemotherapy and its mechanism

Objective: The study was designed to investigate proliferation inhibition for cervical adenocarcinoma HeLa cell treated with cisplatin combined with mifepristone and access its possible mechanism. Materials and Methods: HeLa cell was processed by different concentrations of mifepristone, cisplatin, and their combination respectively. Cell’s proliferation inhibition rate and induction apoptosis ability were detected by MTT assay, FCM; the expression of P53, survivin and HPV E6 protein were measured by Western Blot. Results: The results showed that cisplatin inhibits proliferation of HeLa cells in different concentrations (p < 0.01). Mifepristone had no effect on HeLa cell proliferation inhibition rate during 24 and 48 hours (p > 0.05). Mifepristone at low concentrations (≤ 10 μmol/l) combined with cisplatin can significantly enhance the inhibitory effect of cisplatin on HeLa cell line. Flow cytometry showed that mifepristone at low concentrations (≤ 10 μmol/l) combined with cisplatin can induce apparent apoptosis of HeLa cell line in concentration dependent manner. Western blotting demonstrated that the expression of P53 protein increased and the expression of HPV E6 survivin protein decreased in HeLa cells treated with MIF at low concentrations (≤ 10 μmol/l) combined with cisplatin. Conclusion: Mifepristone at low concentrations (≤ 10 μmol/l) can enhance chemosensitivity and capability of inducing apoptosis of cisplatin to HeLa cells. The strengthening effect of growth inhibition and chemosensitivity to cisplatin of mifepristone are associated with down-regulating HPV E6 survivin protein and upregulating p53 protein.

Mifepristone; Cervical cancer; Cisplatin; Chemotherapy sensitivity.

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