中文摘要：

目的：观察3-溴丙酮酸（3-Bromopyruvic acid,3-Br PA）联合多西他赛（docetaxel,DTX）对乳腺癌MDA-MB-231细胞增殖和凋亡的影响,并探讨相关分子机制。方法：MTT实验检测不同药物处理后乳腺癌MDA-MB-231细胞株存活情况;流式细胞术PI单染法检测用药后细胞凋亡情况;ATP试剂盒检测3-Br PA对细胞内ATP水平的影响;线粒体膜电位检测试剂盒（JC-1）检测3-Br PA对细胞线粒体膜电位的影响;Western blot检测用药后HexokinaseⅡ、Bax、Bcl-2和Mcl-1蛋白的表达情况。结果：3-Br PA、DTX均可抑制MDA-MB-231细胞的生长,呈现浓度依赖性,低浓度3-Br PA明显增强DTX对MDA-MB-231细胞的抑制作用;3-Br PA作用于MDA-MB-231细胞5 h后,随药物浓度递增细胞内ATP水平递减;3-Br PA作用于MDA-MB-231细胞24 h后,HKⅡ表达减少,且使细胞线粒体膜电位发生降低;40μmol/L 3-Br PA联合2μmol/L DTX处理24 h后,MDA-MB-231细胞凋亡率为63.5%,较单独用药组的凋亡率明显提高（P〈0.01）。3-Br PA与DTX联合作用于MDA-MB-231细胞后,凋亡相关蛋白Bcl-2和Mcl-1的表达减弱,Bax的表达增强。结论：3-Br PA可增强DTX对乳腺癌MDA-MB-231细胞的增殖抑制作用以及凋亡诱导作用,其机制可能与下调Mcl-1和Bcl-2表达、上调Bax表达有关。

英文摘要：

AIM： To explore the effect and mechanism of 3-Bromopyruvic acid（ 3-Br PA） combined with docetaxel（ DTX） on the proliferation and apoptosis of MDA-MB-231 cells. METHODS： MTT assay was used to detect the growth inhibition induced by 3-Br PA alone or co-cultured with DTX in MDA-MB-231 cells. Apoptosis was analyzed by flow cytometry with propidium iodide staining（ PI）. ATP levels were detected by ATP assay kit,and the mitochondrial membrane potential was assessed using JC-1 staining assay in the MDA-MB-231 cells. The expressions of protein HK Ⅱ,Bcl-2,Bax and Mcl-1were analyzed by Western blotting. RESULTS： The proliferation of MDA-MB-231 Cells was inhibited by3-Br PA or DTX in a concentration-dependent manner. 3-Br PA in a low concentration enhanced the inhibitory effect of DTX of MDA-MB-231 cells. 3-BrPA treatment MDA-MB-231 cells for 5 h,with the increase of drug concentration,the intracellular ATP levels declined. 3-Br PA lowered mitochondrial membrane potential of MDA-MB-231. When DTX（ 2 μmol/L） was combined with 3-Br PA（ 40 μmol/L）,the cell apoptosis rate increased to 63. 5% after24 h,significantly higher than that in cells with 3-Br PA or DTX treatment alone（ P〈0. 01）. After stimulating with 3-Br PA and DTX,the expression of Bcl-2 and Mcl-1 decreased but expression of bax increased. CONCLUSION： 3-Br PA can enhance the anti-proliferative effect of DTX on MDA-MB-231 cells and enhance DTX-induced apoptosis. The possible mechanism may relate to the down-regulating of Bcl-2 and Mcl-1 expression,and up-regulating of Bax activity.