Cariporide对肿瘤细胞增殖和血管内皮生长因子表达的影响  

Effects of Cariporide on Tumor Proliferation and VEGF Expression

作　　者：李庆华[1] 庞天翔[1] 马丽[1] 李彬 芦颖[1] 李洪强[1] 茹永新[1] 袁文肃[1] 

机构地区：[1]中国医学科学院,中国协和医科大学血液学研究所血液病医院,实验血液学国家重点实验室,300020

出　　处：《天津医药》2007年第11期837-839,共3页Tianjin Medical Journal

基　　金：国家自然科学基金资助项目(项目编号:30570358);天津市自然科学基金资助项目(项目编号:05YFJMJC02100)

摘　　要：目的:探讨特异性抑制剂Cariporide通过抑制钠氢离子交换蛋白1(NHE1)功能而阻止肿瘤细胞增殖的机制。方法:应用四甲基偶氮唑盐(MTT)法检测Cariporide对细胞增殖的抑制率,共聚焦荧光显微镜测算双羧乙基碳氧荧光素四乙酰氧甲酯(BCECF-AM)的荧光强度,检验其下调细胞内pH值,ELISA试剂盒测定其对体外培养细胞表达和分泌血管内皮生长因子(VEGF)的影响,观测其对动物体内肿瘤细胞增殖的抑制作用。结果:随着Cariporide的剂量增加或作用时间延长,HeLa细胞内pH值逐渐降低,肿瘤细胞表达VEGF减少。伴随着细胞内pH值降低,VEGF分泌水平逐渐下降,两者之间呈显著相关性(P<0.05)。另外,Cariporide能抑制动物体内的肿瘤增殖。结论:Cariporide能够减少肿瘤细胞表达和分泌VEGF,抑制动物体内肿瘤增殖。Objective： To investigate the mechanism of special suppressor,Cariporide,by inhibiting the function of Na^＋/H^＋ exchanger 1 to retard the proliferation of tumor cells. Methods： The inhibition ratio of cell proliferation by cariporide was detected by MTT method. The fluorescence of BCECF was detected by confocal microscope and the down regulation effect of Cariporide on intracellular pH of HeLa cells was analyzed. The effects of Cariporide on the expression and secretion of VEGF in vitro were determined by ELISA and its influence on tumor proliferation of animals was observed. Results： The intracellular pH of HeLa cells decreased and the expression of VEGF in tumor cells reduced with the increased action time and dose of cariporide. The decrease of VEGF expression was accompanied with lower level of intracellular pH and it was significant positive correlation with VEGF expression（P 〈 0.05）. Conclusion： Cariporide reduces the expression and secretion of VEGF in tumor cells and suppresses the proliferation of tumor cells of animals.

关 键 词：钠氢反向转运物 血管内皮生长因子类 氢离子浓度 细胞系 肿瘤 肿瘤 细胞增殖 

分 类 号：R541.75[医药卫生—心血管疾病]