CCL19下调β-链蛋白、细胞周期蛋白D1抑制结肠癌  

CCL 19 suppresses proliferation of colon cancer cell via inhibiting β-catenin and cyclin D1 expression

作　　者：关少培 陆军[1,2] 赵敬坤[1,2] 王浦雄志 马君俊[1] 宗雅萍[1] 陈雪华[2] 郑民华[1] 陆爱国[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院外科,上海200025 [2]上海交通大学医学院附属瑞金医院上海消化外科研究所,上海200025

出　　处：《外科理论与实践》2015年第3期236-241,共6页Journal of Surgery Concepts & Practice

基　　金：上海市科委重大引导项目(124119a0900);国家自然科学基金(81201625)

摘　　要：目的:研究趋化因子CCL19对SW1116结肠癌细胞增殖、周期及5-FU疗效的影响。方法 :构建慢病毒LV5-CCL19转染结肠癌细胞株,获得过表达CCL19结肠癌细胞株——SW1116-CCL19。通过细胞增殖实验(CCK-8法)、流式细胞技术、裸鼠体内成瘤实验,分别检测上调CCL19后对SW1116细胞增殖、细胞周期的影响。Western印迹检测细胞内β-链蛋白(β-catenin)、细胞周期蛋白D1(cyclin D1)表达。不同浓度5-FU处理细胞,检测处理后细胞存活率。结果:CCL19上调组SW1116细胞较阴性对照组及空白对照组增殖受抑,同时上调CCL19亦可将细胞周期阻滞在G1期。Western印迹显示CCL19上调组肠癌细胞内β-catenin、cyclin D1较阴性对照组明显降低。上调CCL19可抑制裸鼠皮下肿瘤生长。5-FU作用后,CCL19上调组细胞存活率较阴性对照组降低。结论:CCL19可通过抑制β-catenin、cyclin D1的表达抑制结肠癌的发生发展,提高5-FU的抗肿瘤疗效。Objective To investigate the effect of chemokine CCL19 on proliferation, cycle of colon cancer SW1116 and on enhancing 5-FU treatment. Methods Lentiviral vector was used to transfect CCL19 into colon cancer cell line SW1116 to generate the cell line SW1116-CCL19 with overexpressing CCL19. The effect of CCL19 on the cell proliferation and the cycle were investigated by CCK-8 assay, flow cytometry and nude mouse model. Western blot was performed to detect the expression of potential target β-catenin and its downstream cyclin D1 in SW1116. Several concentrations of5-FU were used to investigate the difference of survival rate between transfected cell line group and negative control group. Results It was shown that overexpressing CCL19 suppressed the proliferation of cancer cell when compared with negative control group and blank control group and arresting of SW1116 was at G1-phase. It was indicated by Western blot that the expressions of β-catenin and cyclin D1 in cancer cell were inhibited in SW1116-CCL19 group compared with those in negative control group. The overexpressing CCL19 inhibited tumor growth in nude mouse study. CCL19 decreased survival rate of cancer cell cultured with 5-FU in overexpressing group compared with negative control group. Conclusions CCL19 suppresses the proliferation and enhances the antitumor effect of 5-FU in colon cancer by inhibiting the expression of β-catenin and cyclin D1.

关 键 词：结肠癌 趋化因子CCL19 Β-链蛋白 氟尿嘧啶 

分 类 号：R735.35[医药卫生—肿瘤]