摘要
目的探讨中链酰基辅酶A脱氢酶(ACADM)对乳腺癌细胞侵袭和转移能力的影响及潜在作用机制。方法采用大型癌症基因组数据库分析ACADM在乳腺癌组织及正常组织中表达量。上调及沉默乳腺癌细胞(MCF-7及T47D)中ACADM的表达,进行体外功能实验(噻唑蓝增殖实验、EdU实验、Transwell小室实验、Boyden体外侵袭实验),探究ACADM对乳腺癌细胞体外增殖、迁移及侵袭能力的影响,通过Western blot检测相关信号通路蛋白表达量,建立裸鼠尾静脉转移模型验证ACADM功能,利用苏木精-伊红染色法诊断肿瘤组织。结果Oncomine样本集提示ACADM的表达水平在乳腺癌组中显著高于正常乳腺组(P<0.05),过表达ACADM可提高乳腺癌细胞(MCF-7、T47D)的迁移和侵袭能力且促进了乳腺癌细胞上皮-间质转化过程,而沉默ACADM后乳腺癌细胞迁移和侵袭能力下降,动物实验进一步验证了ACADM能促进乳腺癌细胞侵袭及迁移能力。结论ACADM可促进乳腺癌细胞上皮-间质转化过程并提高其迁移、侵袭能力,在乳腺癌中扮演促癌基因的角色。
Objective To investigate the effect of medium-chain acyl-CoA dehydrogenase (ACADM) on invasion and metastasis of breast cancer cells and explore the underlying mechanism.Methods A large cancer genome database was used to analyze the expression of ACADM in breast cancer tissues and normal tissues.The proliferation,migration and invasion of cultured breast cancer MCF-7 and T47D cells with ACADM overexpression or ACADM silencing were evaluated using MTT proliferation assay,EdU assay,Transwell chamber assay,and Boyden invasion assay;Western blotting was used to detect the protein expressions of the related pathway in the cells.In nude mouse models of tail vein metastasis of MCF-7 cells with or without ACADM overexpression,the tumor growth and tumor histopathology were observed using HE staining.Results Analysis of the Oncomine sample set showed a significantly higher expression level of ACADM in breast cancer tissues than in normal breast tissues (P<0.05).Overexpression of ACADM obviously enhanced the migration and invasion abilities and promoted the epithelial-mesenchymal transition (EMT) of cultured MCF-7 and T47D cells;conversely,silencing of ACADM significantly suppressed the migration and invasion of the breast cancer cells.In the nude mouse models,ACADM overexpression in MCF-7 cells significantly enhanced their in vivo migration and invasion abilities.Conclusion ACADM can promote the EMT process of breast cancer cells and improve the migration and invasion ability.ACADM is an oncogene in breast cancer.
作者
俞殷珏
赵林丰
李荣
YU Yinjue;ZHAO Linfeng;LI Rong(Department of Oncology,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China)
出处
《南方医科大学学报》
CAS
CSCD
北大核心
2019年第6期650-656,共7页
Journal of Southern Medical University
基金
国家自然科学基金(81772822)
广东省自然科学基金(2017A030313540)~~
关键词
乳腺癌
中链酰基辅酶A脱氢酶
侵袭
迁移
breast cancer
medium chain acyl-CoA dehydrogenase
invasion
migration
