[The enhancement of the chemotherapeutic effects on human prostate cancer cell--the combination with the growth factor interaction inhibitor (suramin)].
The present study was designed to evaluate the antiproliferative effects of suramin and the combination of suramin plus cisplatin (CDDP) on the hormone-independent human prostate carcinoma cell line (PC-93). In vitro, suramin induced a dose-dependent reduction of PC-93 proliferation, and at the clinically achievable concentration (300 micrograms/ml), suramin induced a 19.7% decrease in proliferation on the 3rd day compared to suramin-free control (P < 0.01). However, from the 4th day on the inhibitory action of suramin was reversed following exposure. The suramin-cisplatin combination showed an additive effect (inhibition ratio 32.4% on the 3rd day), and prolongation of the inhibition activity on the 4th day on, but it did not show any synergistic effect. Suramin inhibited dose-dependently the growth stimulatory effect of exogenous epidermal growth factor (EGF). In vivo study, suramin and suramin-cisplatin combination showed antitumor effects continuously in nude mouse implanted PC-93. These findings suggest that the inhibitory effects of suramin on PC-93 are mediated by inhibition of the EGF-mediated growth mechanism, but by a cytostatic rather than cytotoxic manner in vitro. In addition, other mechanisms such as inhibition of angiogenesis factor might exist in vivo.
Suzuki
Y
Y
Department of Urology, Fukui Medical School.
Miwa
Y
Y
Akino
H
H
Fujita
T
T
Saikawa
S
S
Kanimoto
Y
Y
Okada
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004347:Drug Interactions; D004357:Drug Synergism; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000473:pathology*; D013498:Suramin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D013498:Suramin; D002945:Cisplatin