MS-275促进口腔鳞状细胞癌凋亡的实验研究

Experimental study on the apoptosis of oral squamous carcinoma cells induced by MS-275

目的探讨组蛋白去乙酰化酶抑制剂MS-275对口腔鳞状细胞癌(Tca-8113)生长抑制情况以及促进凋亡的作用。方法采用0、0.5、1、2、4、8μmol/L MS-275对口腔鳞状细胞癌进行干预,倒置相差显微镜观察细胞形态改变;MTT法检测细胞增殖活性;Annexin-V-FITC/PI双染流式细胞仪定量检测细胞凋亡,流式细胞仪分析细胞周期。结果①倒置相差显微镜下观察到对照组细胞呈多边形,贴壁,生长活跃;实验组细胞形态改变明显,大部分细胞核固缩,细胞变小、变圆、脱壁。②细胞生长曲线显示,随MS-275浓度增加、时间延长,Tca-8113细胞生长明显受到抑制,各实验组细胞生长抑制率与对照组相比,P<0.05,差别有统计学意义。③2、4μmol/L MS-275作用48h,细胞总凋亡率分别为41.28%和53.71%,细胞周期阻滞于G0/G1期,与对照组相比,差别有统计学意义。结论 MS-275体外抑制口腔鳞状细胞癌生长,呈时间-剂量依赖性,并促进细胞凋亡,阻滞细胞周期。

Objective To investigate the effects of MS-275 on the proliferation of oral squamous cell carcinoma（Tca-8113） and promotion of apoptosis. Methods Oral squamous cell carcinoma was intervened with 0,0.5,1,2,4,and 8μmol/L MS-275,and the morphologic changes of Tca-8113 cells were observed by the inverted phase contrastmicroscope.The cell proliferative activity was measured by MTT assay,the cell apoptotic rates were detected by flow cytometry through Annexin-V-FITC/PI staining,and cell cycles were analyzed by flow cytometry. Results ① Under the inverted phase contrast microscope,no changes of cell morphology could be observed in the control,with cells polygonal,adherent and active.However,the changes could be observed in groups treated with MS-275 at 2,4μmol/L for 48h.The cells became smaller and round,and shrunk cells increased.② A time-and dose-dependent inhibition was detected in Tca-8113 cells that were treated with different concentrations of MS-275 for 24,48 and 72h,with difference of proliferative inhibition between the control and the treated groups（P0.05）.③ Cell apoptosis rate was 41.28% and 53.71% respectively with 2 and 4μmol/L MS-275 treatment for 48h,and cell cycles arrest in G0/G1,with statistical difference. Conclusion MS-275 inhibits the growth of oral squamous cell carcinoma,time-and dose-dependent,and promotes cell apoptosis and blocks cell cycle.