RhoA在缺氧诱导的乳腺癌细胞VEGF分泌和血管内皮细胞增殖、迁移及管腔形成中的作用  

Role of RhoA in hypoxia-induced breast cancer cell VEGF secretion and proliferation,migration and tube formation of HUVECs

作　　者：马骥[1,2] 赵庆丽[1] 任晖[1] 刘文超[2] 薛妍[2] 

机构地区：[1]兰州军区兰州总医院乳腺科,甘肃兰州730000 [2]第四军医大学西京医院肿瘤中心//细胞生物学国家重点学科,陕西西安710032

出　　处：《南方医科大学学报》2012年第6期784-788,共5页Journal of Southern Medical University

基　　金：国家自然科学基金(30770823)~~

摘　　要：目的观察RhoA在缺氧诱导下对乳腺癌细胞MCF-7分泌VEGF水平的影响,以及对人脐静脉内皮细胞HUVEC增殖、迁移和管腔形成的作用。方法 ELISA检测缺氧条件下MCF-7细胞中RhoA的活化与失活对VEGF分泌水平的影响;建立MCF-7/HUVEC共培养模型,观察在缺氧刺激下MCF-7细胞中RhoA活性的变化对HUVEC增殖、迁移和管腔形成的影响。结果缺氧条件下,活性RhoA可以促进MCF-7细胞VEGF分泌,沉默RhoA可以抑制VEGF分泌;在共培养模型中,当MCF-7细胞中RhoA活化时,可以促进HUVEC增殖、迁移和管腔形成,而MCF-7细胞中RhoA沉默时,则HUVEC的上述生物学行为受到抑制。结论在缺氧刺激下,RhoA可能通过调控肿瘤细胞VEGF的表达水平,间接影响HUVEC的增殖、迁移和管腔形成能力,从而参与肿瘤新生血管的形成过程。Objective To explore the role of RhoA in regulating vascular endothelial growth factor （VEGF） secretion level in breast cancer cells and in the proliferation, migration and tube formation of human umbilical vascular endothelial cells （HUVECs） under hypoxia. Methods Enzyme-linked immunosorbent assay was used to examine the effect of V14RhoA plasmid transfection-induced RhoA activation and RhoA knockdown on VEGF secretion level in breast cancer MCF-7 cells under hypoxic condition. A MCF-7/HUVEC co-culture model was established to assess the effect of the changes in RhoA expressions in MCF-7 ceils on HUVEC proliferation, migration, and tube formation under hypoxia. Results Under hypoxic condition, RhoA activation promoted VEGF secretion in MCF-7 cells, and RhoA knockdown inhibited VEGF secretion. In the co-culture model, RhoA activation in the MCF-7 cells enhanced HUVEC proliferation, migration, and tube formation, and RhoA knockdown inhinited these changes. Conclusion Under hypoxic condition, RhoA indirectly influences HUVECs to affect tumor angiogenesis by regulating VEGF level in breast cancer cells.

关 键 词：RHOA 乳腺癌 缺氧 血管内皮生长因子 内皮细胞 细胞增殖 细胞迁移 血管生成 

分 类 号：R737.9[医药卫生—肿瘤] R364.4[医药卫生—临床医学]