Enhancement of antitumor effect of cisplatin against human ovarian carcinoma cells by mifepristone in vivo.

OBJECTIVE

To investigate in vivo the enhancement by mifepristone (RU486) of the antitumor effect of cisplatin (DDP) on human ovarian carcinoma.

METHODS

mouse models bearing xenografted cisplatin-resistant ovarian carcinoma were established, in which the changes in tumor volume and the morphology of the implanted tumors were compared before and after treatment with RU486 and DDP. The expression of glucosylceramide synthase (GcS) mRNA was detected by reverse transcriptase-PCR.

RESULTS

The morphology of the tumors in RU486 plus DDP group was significantly different as compared with that of the control group. In comparison with exclusive DDP treatment, combined treatment with RU486 and DDP resulted in significantly greater inhibition rates of the tumors (70.48% vs 21.55%, P < 0.01). GcS mRNA expression was lowered in both RU486 plus DDP and RU486 groups, especially in the former group, as compared with that in control group.

CONCLUSION

At a non-toxic dose, RU486 may enhance the sensitivity of tumor cells to cisplatin in vivo, possibly through the mechanism of inhibiting GcS expression at the mRNA level.