姜黄素对卵巢癌耐药细胞株COC1/DDP的增敏作用及其机制的研究

ENHANCED SENSITIVITY OF OVARIAN CANCER CELL LINE TO CISPLATIN INDUCED BY CURCUMIN AND ITS MECHANISM

目的：探讨姜黄素对卵巢癌耐药细胞系COC1／DDP的增敏作用并探讨其机制。方法：采用MTT法检测姜黄素对COC1／DDP细胞的增敏作用；用流式细胞仪检测单用顺铂、单用姜黄素、顺铂与姜黄素合用作用于COC1／DDP细胞48h后的细胞凋亡率；Westernblot法检测单用顺铂及顺铂与姜黄素合用后各组细胞凋亡相关蛋白Bcl-2、Caspase-3、Survivin的表达。结果：姜黄素浓度在15～35μmol／L以内时以一定的剂量一效应关系对COC1／DDP有明显的增殖抑制作用。顺铂的浓度在1．25～5mg／L时加入20μmol／L姜黄素后耐药细胞生存率下降明显（P〈0．05），尤以2．5mg／L顺铂和20μmol／L姜黄素联合作用时，耐药细胞生存率下降最明显；COC1／DDP中顺铂与姜黄素联合用药与单独用顺铂及单用姜黄素相比，凋亡率明显增加（P〈0．05）；顺铂与姜黄素联合用药与单独用顺铂相比Bcl-2、Survivin蛋白的表达明显降低（P〈0．05），Caspase-3蛋白的表达明显增高（P〈0．05）。结论：姜黄素能够显著抑制COC-／DDP增殖，并能增强该细胞系对顺铂的敏感性，其机制可能与降低Bcl-2、Survivin蛋白的表达，增加CasDase-3蛋白的表汰有关。

Objective： To observe the effect of Curcumin in enhancing chemosensitivity of drug-resistant ovarian cancer cell line to cisplatin and investigate its mechanism. Methods： The growth inhibiting rates of COC1/ DDP cells by DDP, curcumin, DDP combined with curcumin were studied by methyl thiazolyl tetrazolium （MTT） method; the apoptic ratios of COC1/DDP cells by DDP, curcumin and DDP combined with curcumin were measured by flow cytometry; the expressions of apoptosis-associated proteins Bcl-2, Capase-3, Survivin were studied by Western blot in COC1/DDP cells. Result： 15-35 /μmol/L curcumin could significantly inhibit the growth of COC1/ DDP cells, with the effect depending on concentration of curcumin; 1.25-5 mg/L DDP combined with 20 /μmol/L curcumin could decrease surviving rates of COC1/DDP cells（ P〈0.05）, especially 2.5 mg/L DDP combined with 20 /μmol/L of curcumin. The apoptic ratios of COC1/DDP cells by DDP combined with curcumin were significantly higher than those only by DDP or curcumin （ P % 0.05）. The expressions of Caspase-3 were distinctly higher in DDP combined with curcumin group than that only by DDP at protein level, but Bcl-2 and Survivin significantly lower（ P 〈0.05）. Conclusion： Curcumin can inhibit the growth of COC1/DDP and enhance its sensitivity to DDP. Its mechanism may be associated with over expression protein of Caspase-3 and downregulation protein of Bel-2 and Survivin.