苯丁酸钠对乳腺癌细胞增殖和凋亡的影响

Effects of sodium phenylbutyrate on proliferation and apoptosis of human breast cancer cell

目的观察分析苯丁酸钠(Sodium phenylbutyrate,NaPB)对乳腺癌MDA-MB-231细胞增殖和凋亡的影响,初步探究其可能的作用机制。方法以不同剂量NaPB(0 mmol/L、2 mmol/L和4 mmol/L)处理乳腺癌MDA-MB-231细胞株并进行实验分组:对照组,2 mmol/L NaPB组4 mmol/L NaPB组。采用四甲基偶氮唑盐微量酶反应比色法(MTT法)检测各组乳腺癌细胞的增殖情况,使用流式细胞仪检测细胞凋亡,应用蛋白质印迹法(Western Blot)检测凋亡相关蛋白B细胞淋巴瘤/白血病-2(Bcl-2)、Bcl-2相关X蛋白(Bax)和乳腺癌易感基因1(BRCA1)蛋白表达的水平。结果NaPB能显著抑制乳腺癌MDA-MB-231细胞的生长增殖,并可诱导乳腺癌细胞凋亡,对照组、2 mmol/L NaPB组和4 mmol/L NaPB组乳腺癌细胞的凋亡率分别为(4.25±0.89)%、(14.11±2.98)%和(32.73±1.89)%,两两比较均差异有统计学意义(P<0.05),NaPB可诱导凋亡相关蛋白Bcl-2表达水平下降,而Bax表达水平升高,NaPB的抗肿瘤作用在高剂量组中表现得更明显。与对照组相比NaPB可显著下调BRCA1蛋白的表达,差异有统计学意义(P<0.05)。结论NaPB可抑制乳腺癌细胞增殖和诱导细胞凋亡,其作用机制可能与NaPB下调BRCA1表达有关。

Objective To study the effects of sodium phenylbutyrate(NaPB)on the proliferation and apoptosis of human breast cancer cell Line MDA-MB-231,and to explore the probable mechanism.Methods MDA-MB-231 cells were treated with different concentration of NaPB(0 mmol/L、2 mmol/L and 4 mmol/L),and assigned into control group,2 mmol/L NaPB group and 4 mmol/L NaPB group.Tetramethylazoazole salt microenzyme reaction colorimetric method(MTT)assay was performed to detect the proliferation of MDA-MB-231 cells.The cell apoptosis was tested using flow cytometry.Western Blot assay was carried out to examine the apoptosis-related proteins Bcl-2,Bax and breast cancer gene 1(BRCA1).Results NaPB significantly inhibited the growth and proliferation of breast cancer MDA-MB-231 cells and induced apoptosis of breast cancer cells,the average apoptosis rate in control group,2 mmol/L and 4 mmol/L NaPB group was(4.25±0.89)%,(14.11±2.98)%and(32.73±1.89)%,respectively,and the difference between the two pairs was statistically significant(P<0.05).NaPB decreased the expression level of apoptosis-related protein Bcl-2 and increased the expression level of Bax,and the anti-tumor effect of NaPB was more obvious in the high-dose group.Compared with the control group,NaPB significantly reduced the expression of BRCA1 protein,and the difference was statistically significant(P<0.05).Conclusion NaPB can inhibit breast cancer cell proliferation and induce apoptosis,and its mechanisms may be related to down-regulation of BRCA1expression.