c-IAP1在食管鳞癌中的表达及其对化疗敏感性的影响

c-IAP1 expression and tumor chemosensitivity in esophageal squamous cell carcinoma

目的:探讨食管鳞癌细胞凋亡抑制蛋白1(c-IAP1)表达与化疗敏感性的相关性.方法:食管鳞癌组织芯片免疫组织化学染色,分析食管鳞癌组织及其配对癌旁食管上皮中c-IAP1的表达和定位及其与肿瘤临床分级的关系.免疫印迹分析食管癌细胞c-IAP1和Smac表达,用RNA干扰技术敲降Smac表达,MTT法检测细胞对化疗药物敏感性的影响.统计分析采用卡方检验.结果:与癌旁食管上皮(54%,28/52)相比,c-IAP1在食管癌组织中高表达(67%,35/52),但与肿瘤病理分级、年龄和性别无关.c-IAP1定位于组织细胞质和细胞核,在46%(24/52)的肿瘤组织中,细胞质c-IAP1表达水平显著高于配对癌旁食管上皮4%(2/52),具有统计学意义(P<0.001).食管癌EC0156、KYSE510、KYSE30、KYSE180和KYSE170细胞普遍表达c-IAP1,其中KYSE170细胞表达最高.经RNA干扰敲降Smac分子,可显著降低KYSE170细胞对化疗药物的敏感性.结论:c-IAP1蛋白在食管癌组织细胞质中表达率高,经化疗药物处理后,Smac介导c-IAP1降解,增加了食管癌细胞对化疗药物的敏感性,c-IAP1在调控食管癌化疗敏感性中发挥重要作用.

AIM：To investigate the expression of cellular inhibitor of apoptosis protein 1（c-IAP1）in esophageal squamous cell carcinoma（ESCC）and to evaluate the correlation between c-IAP1 expression and chemosensitivity of ESCC cell lines.METHODS：Immunohistochemistry staining was performed to determine the expression of,c-IAP1 in ESCC on tissue microarray.The chisquare test was used to analyze the correlation between c-IAP1 expression and clinicopathologic parameters of ESCC.The expression of c-IAP1 and Smac in several ESCC cell lines was detected by Western blot.The chemosensitivity of ESCC cell lines was evaluated by RNA interference with Smac gene expression and MTT assay.RESULTS：c-IAP1 expression was found in 67%（35/52）of ESCC tissue specimens and in 54%（28/52）of tumor-adjacent normal tissue specimens.c-IAP1 expression was not correlated with age,gender,tumor stage（all P0.05）.c-IAP1 was localized to both the cytoplasm and nucleus.Cytoplasmic c-IAP1 expression was detected more frequently in ESCC than in tumoradjacent tissue specimens[45%（24/52）vs 4%（2/52）,P 0.001].c-IAP1 and Smac were widely expressed in ESCC cell lines,including EC0156,KYSE510,KYSE180,KYSE170,and KYSE30.Knockdown of Smac significantly reduced chemosensitivity of KYSE170 cell line to anticancer drugs.CONCLUSION：The expression of c-IAP1 was up-regulated in both ESCC cell lines and tumor tissue.Smac mediates the degradation of c-IAP1 after cisplatin treatment.c-IAP1 and Smac might regulate chemosensitivity of ESCC cell lines.