凋亡抑制蛋白在TRAIL诱导胃癌细胞凋亡中的作用

目的探讨凋亡抑制蛋白(inhibitor of apoptosis pro-teins,IAP)在调节胃癌细胞对肿瘤坏死因子相关凋亡诱导配体(tumor necrosis factor-related apoptosis-inducing ligand,TRAIL)敏感性方面的作用。方法 PI染色流式细胞术检测细胞凋亡;Western blot检测caspase-3、PARP、XIAP、Survivin、cIAP1和cIAP2的表达。结果 TRAIL能诱导胃癌细胞凋亡,BGC-823细胞较SGC-7901细胞对TRAIL更敏感。caspase-3的活化及PARP的裂解在TRAIL作用早期即出现,且BGC-823细胞较SGC-7901细胞发生得更快。4种IAP蛋白在两株胃癌细胞中都组成性地高表达,Survivin和cIAP1在TRAIL处理前后无变化。而XIAP在BGC-823细胞中明显下降,在SGC-7901细胞中无改变。cIAP2在TRAIL作用后两株细胞中均有所降低。结论 TRAIL诱导胃癌细胞凋亡可能在活化的caspase-3水平受调控,XIAP能保护胃癌细胞免于凋亡。

Role of inhibitor of apoptosis proteins in TRAIL-induced apoptosis of gastric cancer cells

Aim To explore the role of inhibitor of apoptosis proteins(IAP) in regulating the sensitivity of gastric cancer cells to tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)-induced apoptosis.Methods Apoptotic cells were determined by the propidium iodide method using flow cytometry.The activation of caspase-3 and PARP cleavage were conducted by Western blot analysis.Expressions of XIAP,Survivin,cIAP1 and cIAP2 before and after treatment with TRAIL were also measured by Western blot analysis.Results TRAIL induced apoptosis in gastric cancer cells.BGC-823 cells were more sensitive to TRAIL than SGC-7901 cells.Caspse-3 activation and PARP cleavage were detected early after exposure to TRAIL.IAP family members were constitutively overexpressed in the two cell lines.The expression of XIAP was significantly downregulated in BGC-823 cells,compared with that in SGC-7901 cells,after TRAIL treatment.The expression of Survivin and cIAP1 remained unchanged.The expression of cIAP2 was slightly lowered in the two cell lines.Conclusions TRAIL-induced apoptosis of gastric cancer cells appears to be determined at the level of the effector caspase-3.XIAP protects gastric cancer cells from TRAIL-indued apoptosis.