sFRP2和Wnt/β-catenin通路在结直肠癌发生发展中的作用  

The role of sFRP2 and Wnt/β-catenin pathway in the development and progression of colorectal cancer

作　　者：史友权 崇杨[2,3] 汤东 熊清泉[2,4] 黄玉琴[2,5] 周怀成[2,3] 张琪[2,3] 金芝祥 王道荣[2] Shi Youquan;Chong Yang;Tang Dong;Xiong Qingquan;Huang Yuqin;Zhou Huaicheng;Zhang Qi;Jin Zhixiang;Wang Daorong(Department of General Surgery of Feng Xian People′s Hospital of Jiangsu Province,Xuzhou 221700,China;Department of General Surgery of Subei People′s Hospital of Jiangsu province,Institute of General Surgery,Yangzhou 225001,China;Yangzhou University Medical Academy,Yangzhou 225001,China;Xianya School of Medicine,Changsha 410013,China;Dalian Medical University,Dalian 116044,China)

机构地区：[1]江苏省丰县人民医院普通外科,徐州221700 [2]江苏省苏北人民医院胃肠中心,扬州225001 [3]扬州大学医学院,225001 [4]中南大学湘雅医学院,长沙410013 [5]大连医科大学,116044

出　　处：《中华结直肠疾病电子杂志》2018年第6期531-537,共7页Chinese Journal of Colorectal Diseases(Electronic Edition)

基　　金：重点病种规范化诊疗项目(No.BE2015664)

摘　　要：目的研究分泌型卷曲蛋白2(Secreted Frizzled-related proteins 2,sFRP2)与Wnt/β-catenin通路在结直肠癌发生发展中的作用。方法首先对正常结直肠黏膜组织和结直肠癌组织行免疫组化实验,检测sFRP2及β-catenin的表达水平和阳性率。其次通过质粒转染,使得sFRP2在HCT116细胞中的表达上调,通过Western blot实验验证,然后行CCK-8实验、划痕实验、Transwell实验,分析sFRP2表达上调后对细胞增殖、迁移和侵袭的影响。结果正常结直肠黏膜组中s FRP2阳性表达率显著高于结直肠癌组(X^2=35.902,P=0.000)。相反,结直肠癌组中β-catenin膜表达缺失率和异位表达率显著高于正常结直肠黏膜组(X^2=23.149,P=0.000;X^2=27.002,P=0.000)。sFRP2阳性表达、β-catenin膜表达缺失、异位表达与肿瘤组织分化明显相关(X^2=5.420,P=0.020;X^2=6.472,P=0.011;X^2=7.158,P=0.007),而与性别、年龄、肿瘤部位、肿瘤大小、肿瘤分期和淋巴结转移无关(P> 0.05)。sFRP2的阳性率与β-catenin的膜表达缺失率及异位表达率呈负相关,β-catenin的膜表达缺失率和异位表达率呈正相关。转染后sFRP2及β-catenin表达水平显著升高(t=25.430,P=0.001;t=15.000,P=0.001)。sFRP2转染组与对照组及空载质粒组相比,细胞增殖速度及迁移速度明显减慢(t=16.890,P=0.001;t=7.206,P=0.002)。与对照组相比,sFRP2转染组透膜细胞数明显少于对照组(t=25.459,P=0.001),细胞侵袭能力显著下降。结论 sFRP2与Wnt/β-catenin通路相互作用,在结直肠癌的发生发展中起着重要作用。sFRP2的上调明显抑制了HCT116细胞的增殖、迁移和侵袭。ObjectiveTo explore The role of sFRP2 and Wnt/β-catenin pathway in the development and progression of colorectal cancer. MethodsImmunohistochemical staining was used to detect the expression of sFRP2 and β-catenin in colorectal cancer group and normal colorectal mucosa group, to detect the expression level and positive rate. The expression of sFRP2 gene in colorectal cancer cell line HCT116 was up-regulated by plasmid transfection, it was verifled by Western blot. Then we conduct CCK-8 method, wound-healing assay and Transwell assay. Then the effects of up regulation of sFRP2 expression on cell proliferation, migration and invasion were analyzed. ResultsThe results of immunohistochemistry showed that the positive rate of sFRP2 expression in normal colorectal mucosa is higher than colorectal cancer group （χ2=35.902, P=0.000）; However, The rate of β-catenin membrane expression deficiency and ectopic expression in colorectal cancer group is higher than normal colorectal mucosa （χ2=23.149, P=0.000, χ2=27.002, P=0.000）. The positive expression of sFRP2, the loss of expression and the ectopic expression of β-catenin membrane were significantly correlated with the differentiation of tumor tissues （χ2=5.420, P=0.020, χ2=6.472; P=0.011, χ2=7.158, P=0.007）, however, it was not associated with sex, age, tumor location, tumor size, tumor stage and lymph node metastasis （P 〉 0.05）. The expression of sFRP2 was negatively correlated with β-catenin membrane expression deficiency and ectopic expression; There was a positive correlation between the β-catenin membrane expression deficiency and the ectopic expression. After plasmid transfection, the expression of sFRP2 and β-catenin significantly increased （t=25.430, P=0.001; t=15.000, P=0.001）; The proliferation and migration rate of sFRP2 transfection group was significantly slower compared with the control group and the empty plasmid group （t=16.890, P=0.001; t=7.206, P=0.002）; Compared with the control group, the number of transmembran

关 键 词：结直肠肿瘤 SFRP2 Β-CATENIN HCT116细胞 

分 类 号：R735.34[医药卫生—肿瘤]