凋亡抑制蛋白在TRAIL诱导胃癌细胞凋亡中的作用

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

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。

Aim To explore the role of inhibitor of ap- optosis proteins （lAP） in regulating the sensitivity of gastric cancer ceils to tumor necrosis factor-related ap- optosis-inducing ligand （ TRAIL ） -induced apoptosis. Methods Apoptotic cells were determined by the pro- pidium iodide method using flow cytometry. The acti- vation of caspase-3 and PARP cleavage were conducted by Western blot analysis. Expressions of XIAP, Sur- vivin, 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 sig- nificantly downregulated in BGC-823 cells, compared with that in SGC-7901 cells, after TRAIL treatment. The expression of Survivin and clAP1 remained un- changed. The expression of cIAP2 was slightly lowered in the two cell lines. Conclusions TRAIL-induced apoptosis of gastric cancer ceils appears to be deter- mined at the level of the effector caspase-3. XIAP pro- tects gastric cancer cells from TRAIL-indued apopto- sis.