SAHA和TRAIL联合作用对MDA-MB-231细胞增殖影响  

Synergistic effect of suberoylanilide hydroxamic acid and tumor necrosis factor-related apoptosis-inducing ligand on proliferation of triple-negative breast cancer cell line MDA-MB-231 cells

作　　者：冯秀艳[1,2] 晏林[3] 周伟强[1] FENG Xiu-yan YAN Lin ZHOU Wei-qiang(Key Laboratory of Environmental Pollution and Microecology of Liaoning Province ,Department of Endocrinology,The Second Affiliated Hospital of Shenyang Medical College ,Shenyang ,Liaoning Province 110034, China)

机构地区：[1]沈阳医学院附属第二医院内分泌科,辽宁沈阳110034 [2]辽宁省环境污染与微生态重点实验室 [3]沈阳医学院

出　　处：《中国公共卫生》2017年第3期452-456,共5页Chinese Journal of Public Health

基　　金：国家自然科学基金(81172509);沈阳医学院科技基金(20121003)

摘　　要：目的探讨辛二酰苯胺异羟肟酸(SAHA)与肿瘤坏死因子相关凋亡诱导配体(TRAIL)联合作用对三阴乳腺癌细胞系细胞增殖影响。方法以乳腺癌MDA-MB-231细胞为研究对象,实验设对照、SAHA、TRAIL、SAHA+TRAIL组,应用自动细胞分析仪检测MDA-MB-231细胞活力、细胞凋亡率和细胞周期变化,采用实时定量PCR和固相凋亡抗体芯片技术检测MDA-MB-231细胞凋亡相关因子mRNA和蛋白的表达。结果与对照组(96.6%)比较,SAHA、TRAIL、SAHA+TRAIL组MDA-MB-231细胞活力(分别为82.5%、87.1%、57.6%)明显降低,细胞增殖被明显抑制,SAHA与TRAIL联合应用对MDA-MB-231细胞生长的抑制作用具有协同效应;与对照组比较,SAHA与TRAIL联合应用使MDA-MB-231活细胞比率降低39%,活细胞总数下降超过40%;实时定量PCR和凋亡抗体芯片筛查结果表明,与对照组比较,SAHA与TRAIL联合应用后MDA-MB-231细胞caspase-3、TRAIL DR5以及p21^(CIP1)表达量明显增加,Bcl-2、Bcl-x、p53表达量明显减少。结论 SAHA与TRAIL联合应用对三阴乳腺癌细胞MDA-MB-231生长具有协同抑制作用,其机制可能与激活TRAIL相关细胞凋亡通路,诱导细胞凋亡有关。Objective To explore the synergistic effect of suberoylanilide hydroxamic acid （SAHA） and tumor necrosis factor-related apoptosis-inducing ligand （TRAIL） on proliferation of triple-negative breast cancer MDA-MB-231 cells.Methods Human breast cancer MDA-MB-231 cells were treated with SAHA,TRAIL,and SAHA＋TRAIL,except for the cells of the control group.Viability,apoptosis and cell cycle of the MDA-MB-231 cells were detected with Muse Cell Analyzer.The mRNA and protein levels of related apoptotic factors in MDA-MB-231 cells were determined with real-time PCR and solid phase apoptosis antibody microarray.Results Compared with that of the control group （96.6%）,the cell viability of MDA-MB-231 cells of SAHA,TRAIL,and SAHA＋TRAIL groups were 82.5%,87.1%,and 57.6%,respectively,and were significantly lower.In addition,the results suggested a synergistically inhibitive effect of combined SAHA and TRAIL treatment on the viability of MDA-MB-231 cells;the live ratio was decreased by 39% and the proportion of alive cells was reduced by more than 40% for the MDA-MB-231 cells with combined treatment of SAHA and TRAIL.Real-time PCR and apoptosis antibody array results showed that the combined treatment of SAHA and TRAIL enhanced the activity of caspase-3,TRAIL DR5,and p21CIP1 and reduced the expressions of Bcl-2,Bcl-x,and p53 in breast cancer cells.Furthermore,combined treatment of SAHA and TRAIL activated the cell death pathway related with TRAIL,thereby inducing the apoptosis of MDA-MB-231 cells.Conclusion Combined treatment of SAHA and TRAIL has a synergistically inhibitive effect on proliferation of triple-negative breast cancer MDA-MB-231 cells;the mechanism of the effect may be correlated to the activation of TRAIL related apoptotic pathways and the induction of cell apoptosis.

关 键 词：辛二酰苯胺异羟肟酸(SAHA) 肿瘤坏死因子相关凋亡诱导配体(TRAIL) 三阴乳腺癌 MDA- MB-231细胞 

分 类 号：R394.3[医药卫生—医学遗传学]