米非司酮增加子宫内膜癌细胞对顺铂敏感性的实验研究

Effect of mifepristone on chemosensitivity of human endometrial carcinoma cells to cisplatin

目的:探讨米非司酮作用于人子宫内膜癌HEC-1-B细胞后对顺铂敏感性的影响及可能的作用机制。方法:体外培养人子宫内膜癌HEC-1-B细胞,经不同浓度的米非司酮和顺铂单药或联合作用后,用四甲基偶氮唑蓝比色法(MTT法)测定细胞增殖活性作用、流式细胞仪检测细胞周期、免疫组化方法检测凋亡相关蛋白Bcl-2和增殖相关抗原Ki-67蛋白的表达。结果:1.25mg/L和2.5mg/L的米非司酮对HEC-1-B细胞的增殖无明显影响,其与1.0-4.0mg/L顺铂联合作用后,明显增强顺铂对HEC-1-B细胞的增殖抑制作用(P<0.05)。1.25mg/L和2.5mg/L米非司酮和2.5mg/L顺铂联合作用组与单用2.5mg/L顺铂组比较,HEC-1-B细胞G1期比率明显增高、S期比率明显下降(均P<0.05)。细胞的Bcl-2和Ki-67蛋白的表达水平明显下降(P<0.05)。结论:米非司酮能增强顺铂对子宫内膜癌细胞的增殖抑制作用。其作用机制可能与阻滞细胞周期和调控凋亡相关基因的表达、促进细胞凋亡有关。

Objective ：To investigate the effect and mechanism of mifepristone on chemosensitivity of human endometrial carcinoma ceils to cisplatin. Methods ： Human endometrial carcinoma cell line HEC - 1 - B cells were cultured in vitro. HEC - 1 - B cells were treated with various concentration of mifepristone or cisplatin or both. Cell proliferation was evaluated by MTT assay. The cell cycle of HEC - 1 - B cells was analyzed by PI straining flow cytometry. The expressions of Bcl - 2 and Ki - 67 protein in HEC - 1 - B cells were detected by immunohistochemistry. Results：Mifepristone at concentrations 1.25 mg/L or 2.5 mg/L was not of cytotoxicity to HEC - 1 - B cells,but it significantly increased the cytotoxicity of cisplatin at concentrations 1.0 - 4.0mg/L to HEC - 1 - B ceils （ P 〈 0.05 ）. Mifepristone（1.25mg/L,2.5mg/L） promoted cisplatin（1.0,2.0,4.0mg/L） to induce HEC - 1 - B cells apoptosis, G1 phase cell was significantly higher in combination group than that in single group ,while S phase cell was lower（P 〈 0. 05 ） in comparison. The expression of bcl - 2, ki - 67 protein obviously decreased in combined group. Conclu- sion ： Mifepristone can enhance the effect of growth inhibition of cisplatin on HEC - 1 - B cells. Its mechanism may be related to block the cell cycle and regulate the expression of apoptosis - related gene, and promote apoptosis.