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。

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.

山东省引进国外智力基金资助项目（No.20083700340）。