VEGF和SDF-1/CXCR4在促进卵巢癌细胞侵袭与增殖中的相关作用  

The correlative contribution of VEGF and SDF-1/CXCR4 in ovarian cancer cells invasion and proliferation

作　　者：许静[1] 汪宏波[1] 沈晓燕[1] 张萍德[1] 王泽华[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院妇产科,武汉430022

出　　处：《现代妇产科进展》2007年第5期366-370,共5页Progress in Obstetrics and Gynecology

基　　金：湖北省卫生厅科研基金重点资助课题(No:JX1A07)

摘　　要：目的:研究血管内皮生长因子(VEGF)和趋化因子受体(Cys-X-Cysreceptor4,CXCR4)/配体基质细胞衍生因子-1(stromalcell-derivedfactor1,SDF-1)在卵巢上皮性癌细胞中的表达及其在促进卵巢癌细胞侵袭和增殖中的相关作用,进而探讨SDF-1/CX-CR4信号参与卵巢癌发生发展的相关机制。方法:(1)用Real-timeRT-PCR检测卵巢癌细胞株SKOV3中VEGF及其单克隆抗体anti-VEGF作用前后SDF-1/CXCR4mRNA表达水平的变化;(2)通过transwell小室体外侵袭实验检测VEGF和SDF-1以及anti-VEGF和CXCR4特异性抗体(AMD3100)对SKOV3细胞趋化活性的影响;(3)用MTT法测定VEGF和SDF-1以及anti-VEGF和AMD3100作用前后SKOV3细胞增殖率的变化。结果:(1)VEGF可以上调SDF-1和CXCR4的表达且有明显的剂量依赖性。(2)VEGF和SDF-1均有促进卵巢癌细胞侵袭的作用。VEGF的促侵袭作用具有一定的剂量依赖性且可以被40μg/mlanti-VEGF阻断,SDF-1的作用没有明显剂量依赖性;CXCR4的特异性受体抑制剂AMD3100有阻断VEGF和SDF-1的促侵袭作用。(3)VEGF和SDF-1均有促进卵巢癌细胞增殖的作用。VEGF的作用具有剂量依赖性,其效应可被anti-VEGF阻断,但不被AMD3100阻断,SDF-1的促增殖作用无明显剂量依赖性,其效应可被AMD3100阻断。结论:VEGF和SDF-1对卵巢癌细胞的侵袭和增殖有直接促进作用,并且VEGF可以上调SDF-1/CXCR4的表达。两者与卵巢癌的发生和生物学行为关系密切并协同促进卵巢癌细胞的转移。Objective：To investigate the effects of （vascular endothelial growth factor） VEGF on SDF-1/CXCR4 mRNA expression and their correlative contribution in cell invasion and proliferation in human ovarian epithelial cancer ceil line SKOV3, and try to find out some mechanism of SDF-1/CXCR4 signal in the development of ovarian cancer. Methods： The expression of SDF-1/CXCR4 mRNA was evaluated by real-time RT-PCR in human ovarian epithelial cancer ceil line SKOV3 before and after incubated with VEGF or anti-VEGF. The effects of VEGF,SDF-1 ,anti-VEGF and CXCR4 antagonist （AMD3100） on invasion of SKOV3 ceils into Matrigel were measured using Transweil test. The ceil growth rates of SKOV3 ceil lines before and after incubated with VEGF, SDF-1, anti-VEGF and AMD3100 were determined using MTT（4-methyl thiazolyl tetrazolium）method. Results： （1） The expressions of SDF-1 and CXCR4 mRNA were up-regulated significantly by VEGF in a visible dose dependent manner;（2） Both VEGF and SDF-1 had a direct promotive effect on SKOV3 cell invasion. The effect of VEGF had a conspicuous dose dependent and could be blocked by anti-VEGF or AMD3100. The effect of SDF-1 had no evident dose dependent and could be blocked by AMD3100; （3） Both VEGF and SDF-1 had a direct promotive effect on SKOV3 cell proliferation. The effect of VEGF had some dose dependent and could be blocked by anti-VEGF but not by AMD3100. The effect of SDF-1 had no significant dose-dependent and could be blocked by AMD3100. Conclusions ：These results indicate that VEGF can up-regulate expression of SDF-1 and CXCR4 mRNA,and that both VEGF and SDF-1 have a direct promotive effect on cancer cells invasion and proliferation. VEGF and SDF-1 may play a role in the carcinogenesis and progression of ovarian cancer.

关 键 词：卵巢肿瘤 血管内皮生长因子 基质细胞衍生因子-1 受体 趋化因子 

分 类 号：R737.33[医药卫生—肿瘤]