Suzuki Y, Miwa Y, Akino H, Fujita T, Saikawa S, Kanimoto Y, Okada K
Department of Urology, Fukui Medical School.
Hinyokika Kiyo. 1993 Dec;39(12):1215-20.
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.
本研究旨在评估苏拉明以及苏拉明与顺铂(CDDP)联合用药对激素非依赖性人前列腺癌细胞系(PC - 93)的抗增殖作用。在体外,苏拉明可诱导PC - 93细胞增殖呈剂量依赖性降低,在临床可达到的浓度(300微克/毫升)下,与无苏拉明的对照组相比,苏拉明在第3天可使细胞增殖降低19.7%(P < 0.01)。然而,从第4天起,苏拉明的抑制作用在暴露后发生逆转。苏拉明与顺铂联合用药显示出相加作用(第3天抑制率为32.4%),并且从第4天起抑制活性持续延长,但未显示出任何协同作用。苏拉明可剂量依赖性地抑制外源性表皮生长因子(EGF)的生长刺激作用。在体内研究中,苏拉明以及苏拉明与顺铂联合用药在植入PC - 93细胞的裸鼠中持续显示出抗肿瘤作用。这些发现表明,苏拉明对PC - 93的抑制作用是通过抑制EGF介导的生长机制介导的,但在体外是以细胞抑制而非细胞毒性的方式起作用。此外,体内可能存在其他机制,如抑制血管生成因子。