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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 investigate the combined effects of suberoylanilide hydroxamic acid (SAHA) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on the proliferation of human triple-negative breast cancer cell lines. Methods The breast cancer MDA-MB-231 cells were used as experimental subjects. The control, SAHA, TRAIL and SAHA + TRAIL groups were used to detect the viability, apoptosis rate and cell cycle of MDA-MB- The mRNA and protein expression of apoptosis related factors in MDA-MB-231 cells were detected by real-time quantitative PCR and solid-phase anti-apoptotic antibody microarray. Results Compared with the control group (96.6%), MDA-MB-231 cells in SAHA, TRAIL and SAHA + TRAIL groups showed significantly decreased viability (82.5%, 87.1%, 57.6% Compared with the control group, the combination of SAHA and TRAIL decreased the ratio of viable cells of MDA-MB-231 by 39% and the total number of viable cells decreased by more than 40%. Real-time quantitative PCR And apoptosis antibody chip screening results showed that compared with the control group, the expression of caspase-3, TRAIL DR5 and p21 (CIP1) in MDA-MB-231 cells was significantly increased after the combination of SAHA and TRAIL, while the expressions of Bcl- x, p53 expression decreased significantly. Conclusions The combination of SAHA and TRAIL has a synergistic inhibitory effect on the growth of human breast cancer cell line MDA-MB-231. The mechanism may be related to the activation of TRAIL-related apoptosis pathway and the induction of apoptosis.