曲古抑菌素A和紫杉醇对子宫内膜癌细胞增殖和凋亡的影响

目的: 研究曲古抑菌素A（trichostatin A,TSA）和紫杉醇（paclitaxel, PTX）对人子宫内膜癌细胞株KLE增殖和凋亡的影响。方法：TSA和PTX、卡铂（carboplatin，Carbo） 、多柔比星（doxorubicin，Dox）单独或联合作用于KLE细胞，锥虫蓝法观察药物对肿瘤细胞生长的影响；Annexin V、Hoechst染色和线粒体膜电位检测细胞凋亡；Western blotting检测肿瘤细胞凋亡信号通路中多聚ADP核糖聚合酶（PARP）、半胱天冬氨酸蛋白酶9（caspase9）和乙酰化微管蛋白的表达。结果：PTX、Carbo、Dox和TSA对KLE细胞增殖均有抑制作用，TSA和PTX联用后抑制作用最强。Annexin V染色、Hoechst染色、线粒体膜电位法和PARP、Caspase9的检测显示，单用PTX或TSA均可诱导细胞凋亡, 联合应用产生最强的协同作用。Western blotting和免疫组化分析显示，PTX和TSA均可诱导微管蛋白乙酰化，联合用药后微管蛋白乙酰化明显增加。结论: TSA和PTX联合使用有明显的协同作用，能显著抑制子宫内膜癌KLE细胞生长和诱导细胞凋亡，其机制与激活线粒体凋亡信号通路和增强微管蛋白乙酰化有关。

Effect of trichostatin A and paclitaxel on growth and apoptosis of endometrial carcinoma cells

Objective:To investigate the effect of trichostatin A (TSA) and paclitaxel (PTX) on the growth and apoptosis of human endometrial carcinoma KLE cell line. Methods: KLE cells were cultured in the presence of PTX, doxorubicin, carboplatin, histone deacetylase inhibitor TSA or their combination. The growth curve was obtained by trypan blue exclusion assay and cell counting. Cell apoptosis was observed by Annexin V, Hoechst staining and perturbation of mitochondrial membrane potential. The protein expression of PARP, caspase 9 and tubulin acetylation was detected by Western blotting. Results: Paclitaxel, doxorubicin, carboplatin, and TSA all significant inhibited the growth of KLE cells. PTX and TSA both induced cell apoptosis; the combined treatment with TSA and PTX induced more severe apoptosis. Western blotting and immunohistochemistry analysis demonstrated that TSA and PTX induced acetylation of tubulin, and a combination of both resulted in more severe acetylation of tubulin. Conclusion: The synergy of TSA and PTX can greatly inhibit the growth of KLE cells and induce their apoptosis.