神经细胞黏附分子通过非Wnt依赖的β-catenin途径促进小鼠黑色素瘤细胞增殖  

Neural cell adhesion molecule promotes proliferation of mouse melanoma B16-F0 cells via β-catenin independent of canonical Wnt pathway

作　　者：刘瑞[1] 郝春媛[2] 邓秀玲[1] 杨予白[1] 

机构地区：[1]西安交通大学医学院生理和病理生理学系,陕西西安710061 [2]西安市第一医院心血管内科,陕西西安710002

出　　处：《中国病理生理杂志》2013年第9期1645-1650,共6页Chinese Journal of Pathophysiology

摘　　要：目的:研究神经细胞黏附分子(neural cell adhesion molecule,NCAM)对小鼠黑色素瘤B16-F0细胞增殖的影响及其分子机制。方法:采用RNA干扰在B16-F0细胞中基因沉默NCAM,通过MTT和软琼脂克隆形成实验考察细胞增殖能力的变化;通过小鼠皮下肿瘤移植实验考察体内黑色素瘤生长的变化;使用免疫印迹筛选出受NCAM影响的信号分子,在此基础上使用RNA干扰和高表达实验确定介导NCAM调控增殖的主要信号分子。结果:NCAM基因沉默后B16-F0细胞的增殖能力和克隆形成能力明显降低,细胞在小鼠皮下形成的黑色素瘤的生长也明显受到抑制。其中,β-catenin介导了NCAM对于B16-F0细胞增殖的调控,但NCAM对于β-catenin的调控不依赖于经典的Wnt通路。结论:NCAM通过Wnt非依赖性的β-catenin通路促进小鼠黑色素瘤细胞的增殖。AIM：To investigate the effects of neural cell adhesion molecule （NCAM） on the proliferation of mouse melanoma B16-F0 cells, and to further explore the involved signaling pathways. METHODS：RNA interference was used to silence the expression of NCAM in B16-F0 cells, followd by MTT and soft agar assays to evaluate the proliferation. Subcutaneous transplatation of NCAM-silencing B16-F0 cells into C57BL/6J mice was performed, and the tumor growth in vivo was observed. Western blotting was used to clarify the involved signaling pathways. RESULTS：The proliferation and colony formation of B16-F0 cells in vitro and the growth of transplanted melanoma in vivo were significantly inhibited by NCAM siRNA. Interestingly, the change of NCAM expression level markedly regulated the activity of β-catenin, and this signaling pathway was independent of canonical Wnt pathway. CONCLUSION：Our findings reveal a novel regulatory role of NCAM in the progression of melanoma, which might serve as a new therapeutic target for the treatment of melanoma.

关 键 词：神经细胞黏附分子 黑色素瘤 Β-CATENIN 细胞增殖 

分 类 号：R739.5[医药卫生—肿瘤]