COMPLETE INHIBITION OF HUMAN OVARIAN-CANCER XENOGRAFTS IN NUDE-MICE BY SURAMIN AND CIS-DIAMMINEDICHLOROPLATINUM(II)

In this study, we have determined the adjuvant effects of suramin to c is-diamminedichloroplatinum(II) (CDDP) on human ovarian cancer (KF) ce ll growth in vitro and in vivo. Suramin inhibited the ovarian cancer c ell proliferation in vitro in a dose-dependent manner between 10 and 8 0 mu M, showing the IC50 of 29 mu M. From analysis of flow cytometry ( FCM), suramin seemed to be a blocker of G(2)-M phase of the cell cycle . From the results of the isobologram, suramin appeared to have additi ve and somewhat synergistic effects on antitumor activity of CDDP. Whe n 5 x 10(5) KF cells were inoculated sc into the right flank of nude m ice, 8 of 10 mice formed solid tumor at 4 weeks. When 2 mg/kg CDDP was administered ip every week, the 80% tumor formation was prolonged to 10 weeks. Treatment with 5 and 10 mg/kg suramin decreased the formatio n rate of palpable tumor to 50 and 30%, respectively. When CDDP was fo llowed by 5 or 10 mg/kg suramin, the tumor formation rate was 20 or 0% . On the other hand, if suramin was followed by CDDP, the tumor format ion was not observed in any mouse during the experimental period. Thes e results suggest that suramin may provide a new strategy for treatmen t of refractory ovarian carcinoma. (C) 1995 Academic Press, Inc.