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

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.