米非司酮增加宫颈癌Caski细胞对顺铂敏感性的研究

目的：探讨米非司酮作用于人宫颈鳞癌Caski细胞后对顺铂敏感性的影响和机制。为临床应用米非司酮治疗宫颈鳞癌提供实验依据。方法：体外培养人宫颈鳞癌Caski细胞，分别或联合应用不同浓度的米非司酮、顺铂处理Caski细胞，采用四甲基偶氮唑蓝比色法测定米非司酮对Caski细胞增殖活性的作用及其对顺铂敏感性的影响；流式细胞术观察各组细胞凋亡率，并分析细胞周期的变化；异硫氰酸荧光素（FITC）荧光标记流式细胞术（FCM）法测定米非司酮对Caski细胞HPV—E6，p53，Bcl-2，Bax蛋白的表达变化。结果：四甲基偶氮唑蓝比色法结果显示，1．25、2．5mg／L的米非司酮对Caski细胞无显著的抑制作用，其与顺铂合用时能增强顺铂对Caski细胞增殖抑制作用。流式细胞术结果显示，米非司酮（1．25mg／L）对Caski细胞无明显的诱导凋亡作用，但能促进顺铂（1．0、2．0、4．0mg／L）诱导其凋亡。FITC荧光标记FCM法结果显示，米非司酮作用于Caski细胞后，HPV—E6、Bcl-2蛋白表达下调，p53、Bax蛋白表达上调，呈浓度依赖方式。结论：米非司酮能增强顺铂对Caski细胞的增殖抑制和诱导凋亡并对Caski细胞有增殖抑制和化疗增敏作用，与下调HPV16-E6、Bcl-2蛋白表达，上调p53、Bax蛋白表达有关。

Effect of mifepristone on chemosensitivity of human cervical squamous carcinomacells to cisplatin

Objective To investigate the effect and its mechanism of mifepristone on chemosensitivity of human cervical squamous carcinoma cells to cisplatin and to give experimental basis for cervical squamous carcinoma with mifepristone.Methods Human cervical squamous carcinoma cell line Caski cells were cultured in vitro.Caski cells were treated with various concentration of mifepristone or cisplatin or both.Cell proliferation was evaluated by MTT assay.The apotosis of Caski cells were determined by PI staining flow cytometry and cell cycle was analyzed using flow cytometry.The expression and their activity change of HPV16-E6,p53,Bcl-2,Bax protein in Caski cells were investigated by FITC staining flow cytometry.Results(1) MTT assay indicated that mifepristone at concentrations 1.25,2.5 mg/L was not of cytotoxicity to Caski cells(IR<5%),but it significantly increased the cytotoxicity of cisplatin to Caski cells(q>(1.15)).(2) PI staining flow cytometry data showed the apoptosis of Caski cells could not be induced by mifepristone at concentrateions 1.25,2.5 mg/L,whereas,mifepristone(1.25 mg/L) significantly promoted cisplatin(1.0,2.0,4.0 mg/L) to induce Caski cells apoptosis.(3) FITC staining flow cytometry indicated the expression of HPV16-E6,Bcl-2 protein decreased and the expression of p53 and Bax protein increased in Caski cells treated with mifepristone in a concentrateion dependent manner(P<0.05).Conclusion Mifepristone(1.25,2.5 mg/L) enhances the effect of growth inhibition and apoptosis induction of cisplatin on Caski cells.The effect of chemosensitization to cisplatin of mifepristone on Caski cells is associated with downregulating expression of HPV16-E6,Bcl-2 protein and upregulating expression of p53 and Bax protein.