前立腺癌に対する化学療法効果増強の試み : Growth factor interactionのInhibitorとの併用

Abstract

1)ヒト前立腺癌株PC-93を用いてin vitroならびにin vivoでsuraminの抗腫瘍効果とCDDPとの併用効果を検討した。2)in vitroではsuramin単独は臨床使用可能な濃度では十分な増殖抑制効果はえられなかった。その効果はcytostaticであった。3)CDDPとの併用では増殖抑制効果の延長と相加効果を認めた。4)suraminはEGFによるPC-93の細胞増殖促進効果を抑制した。5)ヌードマウスを用いた検討ではsuraminは持続的抗腫瘍効果を示し, CDDP併用により効果増強を認めた

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.