YAP在结直肠癌中的表达及对结直肠癌增殖的影响  

Expression of Yes-associated protein in colorectal carcinoma and its effect on tumor cell proliferation

作　　者：曹伟军[1] 徐亦君[1] 徐兆军[1] 袁捷[1] 张振玉[1] 

机构地区：[1]南京医科大学附属南京医院南京市第一医院消化内科,南京210006

出　　处：《中国医师杂志》2013年第7期885-889,共5页Journal of Chinese Physician

基　　金：南京医科大学科技发展基金资助项目（2010NJMU042）

摘　　要：目的观察Yes相关蛋白（YAP）在结直肠癌中的表达，并分析其对结直肠癌细胞增殖的影响。方法收集结直肠癌组织及癌旁正常组织各94例，采用免疫组化方法检测YAP蛋白的表达。利用siRNA降低结直肠癌细胞HCTl16中YAP的表达，运用MTT比色法检测结直肠癌细胞增殖的变化。结果YAP蛋白在结直肠癌组织中的阳性率为69．1％（65／94），明显高于癌旁正常组织的22．3％（21／94），差异有统计学意义（P〈0．001）。YAP蛋白的表达与结直肠癌的TNM分期及淋巴结转移有关（P〈0．05），而与患者性别、年龄、肿瘤部位及分化程度无关（P〉0．05）。利用脂质体将靶向YAP的siRNA转染HCTll6后，实验组YAPmRNA和蛋白表达量分别下降（78．2±2．1）％和（81．7±1．5）％，差异有统计学意义（t=67．55，91．601，P〈0．01）；HCTll6的增殖受到显著抑制，48、72、96h实验组的细胞生长抑制率分别为（28．1±1．6）％、（34．7±2．4）％、（24．7±1．2）％。结论YAP在结直肠癌中高表达，降低其表达能显著抑制结直肠癌细胞的增殖。YAP可作为结直肠癌分子诊断和基因治疗的一个新的候选靶点。Objective To evaluate the expression of Yes-associated protein （YAP） in colorectal carcinoma and analyze its influence on tumor cell proliferation. Methods The expressions of YAP in 94 paired colorectal carcinomas and pericancerous normal tissues were detected by using immunohistochemistry method. The expressions of YAP in colorectal carcinoma cell line HCTll6 were inhibited with a YAP-spe- cific siRNA. Cell proliferation was then determined by methyl thiazolyl diphenyl-tetrazolium bromide （M＇Iq＇） assay. Results The positive rate of YAP in colorectal carcinomas was significantly higher than that in pericancerous normal tissues [ 69. 1% （65/94） vs 22. 3 % （21/94）, P 〈 0. 001 ]. The expression of YAP was associated with tumor Node Metastasis（TNM） stage and lymph node metastasis （ P 〈 O. 05 ）, but not associated with gender, age, tumor location and histological grade （ P 〉 0. 05）. After YAP- specific siR- NA was transfected into HCTll6 using lipofectamine, the expression of YAP mRNA and protein in the ex- perimental group were reduced by （78. 2 ± 2. 1 ） % and （ 81.7± 1.5） %, respectively, with a statistically significant difference （ t = 67. 55, 91. 601, P 〈 0. 01 ）. The growth of HCT116 was significantly inhibited and the reduced rate of cell proliferation was （28.1 ± 1.6） %, （34. 7 ±2.4） % and （24. 7 ± 1.2） % at the time point of 48 h, 72 h and 96 h, respectively. Conclusions Expression of YAP was upregulated in colo- rectal carcinomas and downregulation of YAP expression could inhibit growth of colorectal carcinoma ceils. YAP can be used as a new candidate target for diagnosis and treatment of a colorectal carcinoma.

关 键 词：结直肠肿瘤 病理学 细胞增殖 RNA干扰 

分 类 号：R735.3[医药卫生—肿瘤]