选择性环氧合酶抑制剂celecoxib对血管平滑肌细胞的增殖抑制、凋亡诱导作用和分子机制

Celecoxib inhibits proliferation and induces apoptosis in vascular smooth muscle cells with its molecular mechanism

目的:探讨环氧合酶-2(COX-2)选择性抑制剂塞莱昔布(celecoxib)对血管平滑肌细胞的增殖抑制作用及分子机制。方法:给予原代培养的大鼠平滑肌细胞不同浓度的celecoxib处理,WST-1细胞增殖实验观察细胞的生长抑制作用;流式细胞术检测凋亡;Western blot方法检测血管平滑肌细胞COX-2的表达、caspase-3蛋白的裂解激活、磷酸化Akt的表达。结果:WST-1实验结果显示,经0、6.25、12.50、25.00、50.00μmol/Lcelecoxib作用24h后,细胞的增殖率分别为100%、81.15%、66.72%、54.93%和11.41%;50μmol/L celecoxib作用24h后,流式细胞仪检测细胞凋亡率为30.72%;Western blot实验显示,血管平滑肌细胞中COX-2有表达,celecoxib作用于细胞后caspase-3蛋白裂解片段激活,磷酸化Akt的表达减弱或消失。结论:celecoxib对血管平滑肌细胞有增殖抑制和凋亡诱导作用,其机制可能部分涉及到Akt/caspase途径。

Objective：To investigate the cell growth inhibition induced by selective cyclooxygenase-2（COX-2） inhibitor celecoxib and its molecular mechanisms. Methods：Cell growth rates were assessed by WST-1 assay. Apoptosis was examined by flow cytometry. The expression of COX-2, caspase-3 and Akt phosphorylation were examined by western blot analysis. Results：Cells were treated with increasing concentrations of celecoxib （0-50μmol/L） for 24 hours, and the cell growth rate was 100%, 81.15%, 66.72%, 54.93% and 11.41%, respectively. The apoptocic ration of 50 μmol/L group was 30.72%. The remarkable activation of caspase-3 and significant reduction of Akt （Thr308） phosphorylation could be observed by western blotting. Conclusion：The celecoxib inhibited proliferation and induced apoptosis of the vascular smooth muscle cells in a dose dependent manner, which is partly related to the mechanism of Akt/caspase pathway.