组蛋白去乙酰化酶抑制剂曲古抑菌素A对肿瘤多药耐药细胞敏感性的影响  

Study of Histone Deacetylase Inhibitor Trichostatin A on the Sensitivity of Multidrug Resistance Cells

作　　者：周晓平 赵璐[1] 李丹妮[1] 邹鹏[1] 

机构地区：[1]沈阳医学院,辽宁沈阳110016

出　　处：《生物技术通讯》2017年第4期460-464,共5页Letters in Biotechnology

基　　金：沈阳医学院优秀人才启动基金(20103053)

摘　　要：目的:探讨组蛋白去乙酰化酶抑制剂曲古抑菌素A(TSA)对肿瘤多药耐药细胞敏感性的影响。方法:采用MTT法观察TSA对敏感细胞MCF7和多药耐药细胞MCF7/DOX存活率的影响;采用琼脂糖凝胶电泳、Western印迹和实时荧光定量PCR观察DNA梯带形成和凋亡相关蛋白的表达以及乙酰化H3和H4的表达。结果:TSA浓度为20~200 nmol/L时,MCF7组细胞存活率均显著高于MCF7/DOX组,当TSA浓度为50和100 nmol/L时差异最为显著;琼脂糖凝胶电泳表明,TSA浓度为50和100 nmol/L时,与MCF7组相比,MCF7/DOX组产生了更显著的DNA梯带,同时caspase-6及凋亡标志蛋白PARP表达水平高于MCF7组;2株细胞中乙酰化H4和H3没有显著差别,实时荧光定量PCR检测得到相同结果。结论:组蛋白去乙酰化酶抑制剂TSA通过激活caspase-6促进多药耐药细胞MCF7/DOX凋亡而抑制其增殖,与MCF7相比,TSA对MCF7/DOX细胞更为敏感,但原因并非H3、H4乙酰化的差异表达。TSA具有克服肿瘤细胞多药耐药性的应用前景。Objective： To investigate the effect and molecular mechanism of histone deacetylase inhibitor trichostatin A（TSA） on the sensitivity of muhidrug resistance cells. Methods： The cell viability of MCF7 and human breast cancer doxorubicin-resistant MCF7/DOX cells were tested by MTT. The DNA ladder, apoptosis protein ex- pression and acetylation H3 and H4 expression were tested by agarose gel electrophoresis, Western blot and realtime fluorescence quantitative PCR. Results： The cell survival rate of MCFT/DOX group was significantly higher than that in the MCF7 group under 20~200 nmol/L TSA, especially 50 and 100 nmol/L TSA. Compared to MCF7 group, the DNA ladder was significantly increased under the 50 and 100 nmol/L TSA. When the concentration of TSA was 50 and 100 nmol/L TSA, the protein expression level of caspase-6 and PARP elevated more significantly in the MCF7/DOX group than that in the MCF7 group. The expression level of H4 and H3 acetylation had no significantly difference. Conclusion： Histone deacetylase inhibitor TSA inhibited cell viability of MCF7/DOX through activation of caspase-6. Compared with MCF7, TSA is sensitive to MCF7/DOX, but the reason for which is not the different expression of H3, H4 acetylation. TSA has the potential to be applied in the treatment of multi drug resistance.

关 键 词：组蛋白去乙酰化酶 曲古抑菌素A 肿瘤多药耐药细胞 

分 类 号：Q25[生物学—细胞生物学]