肿瘤防治研究2012，Vol.39Issue(10)：1170-1175,6.DOI:10.3971/j.issn.1000-8578.2012.10.003
缺氧及HIF-1α对结直肠癌上皮-间质转化及侵袭增殖的影响
Effect of Hypoxia and HIF-1α on Epithelial-mesenchymal Transition, Invasion and Proliferation in Colorectal Cancer
摘要
Abstract
Objective To study the expression level of the hypoxia inducible factor-1α( HIF-1α) ,zinc finger transcription factor Snail and E-cadhcrin in different hypoxia condition in the colorcctal cancer SW480 cells,and to explore their effect on the proliferation, apoptosis, invasion and transference, approach the roles and mechanisms of them three in the hypoxia and epithelial-mesenchymal transition of colorectal cancer. Methods Chemical was used to induce the cell hypoxia model by cobalt chloride (CoCl2 ) , and three groups: normoxia group, hypoxia group and non-oxygen group were involved in (his study. Methyl thiazolyl tetrazolium(MTT) method was used to detect the proliferativc of colorectal cancer SW480 cells, extraorgan invasion experiment( Transwell method) was applied to evaluate the invasion and transference capability of cells, the cell cycle and apoptosis was examined by flow cytometry(FCM) , the mRNA and protein expression levels of HIF-1α,Snail and E-cadherin were detected by real time PCR(RT-PCR) and Western blot. Results MTT disclosed that the proliferative activity of the colorectal cancer SW480 cells was increased gradually following the concentration increase of the cobalt chloride(P<0. 05) ; transwell showed that the cells permeated the matrix membrane and polycarbonate membrane was increased gradually accompanied with the degree of hypoxia(P<0. 05) ;FCM revealed that in hypoxia group and non-oxygen group,the cells in G0/G1 period was decreased obviously,the cells in G2/S period was increased obviously,the cells apoptosis was dcgradc(P<0. 05) compared with normoxia group;RT-PCR and Western blot displayed that hypoxia group and non-oxygen group compared with normoxia group,the mRNA and protein level of HIF-1α and Snail in SW480 cells was increased,the mRNA and protein of E-cadhenn was decreased(P<0. 05) Furthermore, HIF-1α and Snail had positive correlation,and they had negative correlation with E-cadherin conspicuously(P<0. 05). Conclusion The hypoxia and HIF-1α can promote the extraorgan proliferation activity of the colorectal cancer SW480 cells,inhibit its apoptosis and enhance its extraorgan invasion and migration. The possible mechanism is that hypoxia induced HIF-1α affect SW480 directly,or the hypoxia and HIF-1α expression promote Snail expression and inhibit E-cadherin expression, which lead to EMT and take it place.关键词
缺氧诱导因子-1α/缺氧/上皮-间质转化/Snail/上皮钙黏蛋白Key words
HIF-1a/ Hypoxia/ Epithelial-mesenchymal transit ion (EMT)/ Snail/ E-cadherin分类
医药卫生引用本文复制引用
周明利,卢先州,张留柱,向晶,谢荣俊,肖帅,张树友..缺氧及HIF-1α对结直肠癌上皮-间质转化及侵袭增殖的影响[J].肿瘤防治研究,2012,39(10):1170-1175,6.基金项目
湖南省衡阳市科技局支持项目(2010kj50) （2010kj50）
