凋亡抑制蛋白2在胰腺癌中的表达及其与化疗耐药的关系

目的 观察细胞凋亡抑制蛋白2(c-IAP2)在胰腺癌组织中的表达,探讨c-IAP2表达与胰腺癌细胞对化疗药物耐药性的关系.方法 收集胰腺癌标本32例,应用免疫组织化学染色法观察c-IAP2在胰腺癌及癌旁正常胰腺组织中的表达;体外培养胰腺癌细胞PANC-1,间歇浓度递增法诱导胰腺癌细胞株PANC-1对吉西他滨(Gem)的耐药,噻唑蓝(MTT)检测处理前后细胞对Gem的药物敏感性,免疫荧光和免疫印迹检测c-IAP2蛋白表达水平.结果 c-IAP2在胰腺癌组织均有表达(32/32,100.0%)、癌旁正常胰腺组织(8/18,44.4%)中有表达,胰腺癌表达水平显著强于癌旁正常胰腺组织.c-IAP2的表达强度在不同分化程度的肿瘤组织中的差异有统计学意义(P<0.05).药物培养3个月后,PANC-1对Gem的半数有效浓度(IC50)由(6.03±0.27)mg/L升高至(41.60±1.14)mg/L(P<0.05),免疫荧光和免疫印迹结果显示耐药亚株c-LAP2蛋白表达水平较亲本株升高,差异有统计学意义(P<0.05).结论 C-IAP2在胰腺癌分化程度和对吉西他滨耐药过程中有一定作用.

The relationship between the cell inhibitor of apoptosis protein 2 and chemoresistance in pancreatic cancer

Objective To investigate the expression of cell inhibitor of apoptosis protein 2(c-IAP2) in pancreatic cancer tissues and its clinical significance,and further study the relationship between c-LAP2 and chemoresistance of pancreatic cancer cells. Methods C-IAP2 expression was examined in 32 cases of pancreatic carcinoma by using immunohistochemistry,and the relationship between c-IAP2 expres-sion and clinicopathology analyzed. A gemcitabine-resistant pancreatic cancer cell line (PANC-1) was ob-tained by gradient increase of concentration. The sensitivity of drug resistance was observed by MTT assay. C-IAP2 expression was detected by immunofluorescence and Western blot in pancreatic cancer cell line. Results C-IAP2 expression was detected in 100.0% (32/32) of pancreatic carcinoma tissues and 44. 4% (8/18) of normal pancreatic tissues, respectively. The expression level of c-IAP2 was higher in pan-creatic carcinoma than in normal pancreatic tissues. Significant correlation was found between the expres-sion of c-IAP2 and tumor differentiation (P<0.05). Three months after being cultured by gemcitabine, the ICS0 of PANC-1 cells was increased from (6.03±0.27) to (41.60±1.14) mg/L (P<0.05). C-IAP2 protein expression levels detected by immunofluorescence and Western blot were significantly in-creased in PANC-1/Gem compared to its parental cell line (P<0.05). Conclusion C-IAP2 may play a role in th the differentiation of pancreatic carcinoma and acquired gemcitabine resistance in pancreatic cancer cell line.