目的 探讨TSA对乳腺癌MDA-MB-231细胞增殖、凋亡的影响及作用机制。 方法 采用MTT、克隆形成、流式细胞术检测TSA对乳腺癌MDA-MB-231细胞生物学功能的影响；Western Blot 和qRT-PCR 检测细胞增殖、凋亡和MAPK信号通路蛋白及mRNA 的表达水平的影响；抑制JNK通路检测可能的作用机制。 结果 TSA呈剂量依赖性抑制细胞增殖和诱导凋亡，使细胞阻滞于G1期；TSA可上调P21、Caspase-3、Bax、p-JNK蛋白及mRNA表达，下调Cyclin D1、Cdk4、Bcl-2蛋白及mRNA表达；抑制JNK通路后，p-JNK蛋白和细胞总凋亡率降低，Caspase-3、Bax蛋白及mRNA表达减少，Bcl-2蛋白及mRNA表达增多。 结论 TSA通过MAPK信号通路介导JNK的磷酸化，调控乳腺癌MDA-MB-231细胞的凋亡。
Objective To explore the effect and mechanism of Trichostatin A (TSA) on the cell proliferation and apoptosis of breast cancer MDA-MB-23. Methods MTT, plate cloning experiments, flow cytometry were used to detect the effect of TSA on cell biological functions. qPCR and Western blot were applied to detect the effect of TSA on proliferation, apoptosis and MAPK signaling pathway. Mechanisms were detect by JNK pathway inhibitor in treatment. Results TSA inhibited the proliferation and apoptosis of breast cancer MDA-MB-231 cells in a dose-dependent manner; TSA could block the cell cycle of breast cancer MDA-MB-231 cells in G1 phase. TSA could upregulate the expression of protein and mRNA on P21, caspase-3, Bax and p-JNK, and down-regulate the expression of protein and mRNA of cyclin D1, Cdk4 and Bcl-2. The inhibition of JNK pathway inhibited the expression of p-JNK and the total apoptosis rate of MDA-MB-231 cells. The expression of Caspase-3, Bax and Bcl-2 decreased. Conclusions TSA can induce the apoptosis of MDA-MB-231 cells, the mechanism of which is to regulate the expression of apoptotic protein and induce apoptosis through phosphorylation of JNK in MAPK signaling pathway.
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