染料木黄酮对卵巢癌HO-8910PM裸鼠移植瘤的抑制作用

Inhibitory effect of genistein on human ovarian cancer cell line HO-8910PM in nude mice

目的观察植物雌激素染料木黄酮(GEN)与顺铂(DDP)联合应用治疗人卵巢癌裸鼠移植瘤的效应及其机制.方法建立20只人卵巢癌裸鼠移植瘤模型,随机分成4组,分别为对照组、GEN组、DDP组及GEN+DDP组.4wk后处死裸鼠,计算抑瘤率,用Ⅷ因子抗原多克隆抗体测定肿瘤内微血管密度(MVD),用细胞增殖指数(PI)反映细胞增殖状态,并进行形态学观察.结果DDP组及GEN组均可有效抑制卵巢癌移植瘤生长,二者联合应用有协同作用.GEN+DDP组MVD和PI低于GEN组和DDP组(P<0.01),3组均显著低于对照组(P<0.01).形态学观察可见GEN组和GEN+DDP组细胞凋亡、凋亡小体及变性坏死增多,而对照组少见.结论GEN对人卵巢癌HO-8910PM细胞裸鼠移植瘤有明显抑制作用,且与DDP有协同作用;GEN对肿瘤细胞的作用,与抑制肿瘤细胞的增殖和肿瘤区新生血管的生长、阻断肿瘤血供有关.

AIM： To investigate the effects and possible mechanisms of genistein （ GEN ）, a kind of phytoestrogens, combined with cisplatin （DDP） on human ovarian cancer cells in nude mice. METHODS： Ovarian cancer cell line HO-8910PM derived from human ovarian serous ad was transplanted into 20 nude mice, which were then randomized equally into 4 groups ： GEN treatment group, DDP treatment group, DDP plus GEN treatment group, and a control group. Four weeks later, the body mass of the nude mice was recorded and the morphology of tumor cells was observed by microscope. The expressions of PCNA and microvascular density （MVD） were examined by immunohistochemistry. RESULTS： GEN and DDP effectively inhibited the growth of human ovarian cancer cells transplanted into nude mice and the inhibitory effect was enhanced with combination of GEN and DDP. The expressions of PI and MVD in GEN plus DDP group were lower than those in GEN group or DDP group, which however were lower than those in control group （ P 〈 0.01 ）. The morphological changes in condensation and margination of nuclear chromatin, apoptotic bodies and cell necrosis significantly increased in GEN group and GEN plus DDP group. CONCLUSION： Both DDP and GEN can inhibit the growth of transplanted human ovarian cancer cells in nude mice and exert synergistic anti-tumor effect. The anticancer mechanism of GEN may involve suppressing the proliferation of ovarian cancer cells and angiogenesis and blocking the blood supply of the tumor.