曲古抑菌素A通过上调KLF4表达诱导人子宫内膜癌Ishikawa细胞凋亡  

Trichostatin A induces apoptosis of endometrial cancer Ishikawa cells by up-regulating expression of Krupell-like factor 4

作　　者：赵智凝[1,4] 周强 白久旭[1] 闫博[2] 秦炜炜[2] 王涛[1] 贾林涛[2] 杨安钢[1] 

机构地区：[1]第四军医大学基础医学部免疫学教研室,肿瘤生物学国家重点实验室,陕西西安710032 [2]第四军医大学基础医学部生物化学与分子生物学教研室,陕西西安710032 [3]第四军医大学口腔医院综合急诊科,陕西西安710032 [4]解放军第451医院临床实验室,陕西西安710054

出　　处：《中国肿瘤生物治疗杂志》2012年第1期52-55,共4页Chinese Journal of Cancer Biotherapy

基　　金：国家重点基础研究发展计划(973计划)资助项目(No.2010CB529905)~~

摘　　要：目的:观察组蛋白乙酰基转移酶(histone deacetylase,HDAC)抑制剂曲古抑菌素A(trichostatin A,TSA)对子宫内膜癌Ishikawa细胞凋亡的影响,并研究其与Krupell样因子4(Krupell-like factor 4,KLF4)的关系。方法:0、50、100、200、300、500ng/ml TSA作用于Ishikawa细胞24 h,或100 ng/ml TSA作用于Ishikawa细胞0、4、8、12、24、48 h,流式细胞术检测Ishikawa细胞凋亡情况,qRT-PCR检测Ishikawa细胞中KLF4 mRNA的表达情况;将KLF4真核表达载体pcDNA3-KLF4转染Ishikawa细胞,流式细胞术检测Ishikawa细胞凋亡情况。结果:100 ng/ml TSA作用于Ishikawa细胞24 h后,Ishikawa细胞的凋亡率显著高于对照组[(30.6±4.5)%vs(7.53±0.93)%,P<0.05];不同质量浓度TSA处理Ishikawa细胞24 h后或100 ng/ml TSA作用Ishikawa细胞不同时间后,KLF4 mRNA表达水平以剂量依赖和时间依赖方式明显增高(P<0.05);pcDNA3-KLF4转染后Ishikawa细胞凋亡率显著增加[(27.3±2.7)%vs(4.53±1.75)%,P<0.05]。结论:TSA能通过诱导子宫内膜癌Ishikawa细胞中KLF4的表达,促进Ishikawa细胞发生凋亡。Objective： To observe the effect of Trichostatin A（TSA） on the apoptosis of endometrial cancer Ishikawa cells and to study its relationship with Krupell-like-factor 4（KLF4） in this course.Methods： Ishikawa cells were cultured with different concentrations of TSA 0,50,100,200,300,500 ng/ml for 24 h or 100 ng/ml TSA for 0,4,8,12,24 and 48 h.FACS and qRT-PCR were used to detect apoptosis and KLF4 mRNA level,respectively.Results： The apoptosis rate was increased compared to the control in the Ishikawa cells treated with 100 ng/ml TSA for 24 h（[30.6±4.5]%vs [7.53±0.93]%,P0.05）.The mRNA levels of KLF4 were up-regulated after Ishikawa cells were stimulated with different concentrations of TSA for 24 h or with 100 ng/ml TSA for 4,8,12,24,48 h（P0.05）.Those effects were in a dose-dependent or time-dependent manner.The apoptosis rate was increased compared to the control in the Ishikawa cells over-expressed KLF4（[27.3±2.7]% vs [4.53±1.75]%,P0.05）.Conclusion： TSA induces apoptosis of Ishikawa cells by up-regulating the expression of KLF4.

关 键 词：曲古抑菌素A 子宫内膜癌 ISHIKAWA细胞 Krupell样因子4 凋亡 

分 类 号：R737.33[医药卫生—肿瘤] R730.54[医药卫生—临床医学]