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 cis-diamminedichloroplatinum(II) (CDDP) on human ovarian cancer (KF) cell growth in vitro and in vivo. Suramin inhibited the ovarian cancer cell proliferation in vitro in a dose-dependent manner between 10 and 80 microM, showing the IC50 of 29 microM. From analysis of flow cytometry (FCM), suramin seemed to be a blocker of G2-M phase of the cell cycle. From the results of the isobologram, suramin appeared to have additive and somewhat synergistic effects on antitumor activity of CDDP. When 5 x 10(5) KF cells were inoculated sc into the right flank of nude mice, 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 formation rate of palpable tumor to 50 and 30%, respectively. When CDDP was followed 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 formation was not observed in any mouse during the experimental period. These results suggest that suramin may provide a new strategy for treatment of refractory ovarian carcinoma.
Kikuchi
Y
Y
Department of Obstetrics and Gynecology, National Defense Medical College, Saitama, Japan.
Hirata
J
J
Hisano
A
A
Tode
T
T
Kita
T
T
Nagata
I
I
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005260:Female; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology*; D013498:Suramin / Q000494:pharmacology*
D013498:Suramin; D002945:Cisplatin