组蛋白去乙酰化酶抑制剂SAHA抑制乳腺癌细胞MDA-MB-435增殖及促凋亡的作用机制

目的 观察组蛋白去乙酰化酶抑制剂SAHA对人乳腺癌细胞系MDA-MB-435增殖、凋亡等的作用及其相关分子机制。方法 不同浓度的SAHA作用于MDA-MB-435细胞后，采用MTT、流式细胞分析、Western blot、荧光定量PCR等方法检测细胞增殖、凋亡、周期阻滞情况及相关蛋白及mRNA表达。 结果 MTT检测结果表明SAHA可呈剂量依赖性抑制细胞增殖，流式细胞分析发现SAHA可导致G2/M期周期阻滞、线粒体膜电位下降、活性氧（ROS）产生并发生早期凋亡。同时，SAHA可下调周期蛋白cyclinB、活化p38-MAPK及JNK，抑制p53的表达且可能不是通过PI3K通路、P38 MAPK通路、ERK1/2通路和NF-κB 、JNK通路起作用。结论 SAHA能抑制MDA-MB-435细胞增殖，诱导其周期阻滞及早期凋亡，活化细胞内相关增殖分子，可作为乳腺癌潜在的候选药物。

Effect of SAHA on Proliferation and Apoptosis of Breast Cancer Cells MDA-MB-435 and Related Mechanism

Objective To investigate the effects of SAHA on the proliferation and apoptosis of human breast cancer cells MDA-MB-435 and related mechanisms. Methods After the treatment with different concentrations of SAHA, the proliferation, apoptosis, cell cycle arrest and protein expression of MDAMB-435 cells were detected by MTT, FCM, Western blot and RT-PCR, respectively. Results MTT results showed that SAHA could inhibit cells proliferation in a dose-dependent manner, and FCM analysis showed that SAHA could induce G2/M cell cycle arrest, downregulate mitochondria membrane potential, produce ROS and induce early apoptosis. Moreover, SAHA could downregulate cell cycle protein cyclin B, activate p38-MAPK and JNK, and inhibit P53 expression, and may not be via PI3K, P38 MAPK, ERK1/2, NF-κB or JNK pathways. Conclusion SAHA could inhibit the proliferation, induce cell cycle arrest and early apoptosis, and activate relative cell proliferation molecules in MDA-MB-435 cells, which suggesting that SAHA could be the drug candidate to breast cancer.