阿司匹林对胰腺癌细胞周期的影响及其机制

Effects of aspirin on cell cycle in pancreatic carcinoma cells

目的:观察阿司匹林及其催化产物前列腺素E2(PGE2)对胰腺肿瘤细胞周期及细胞周期相关蛋白p21^(Wafl/cipl)、p27^(Kipl/pic2)表达的影响,探讨阿司匹林抗胰腺癌的作用机制。方法:以阿司匹林和PGE2处理胰腺癌细胞后,分别采用MTT检测细胞活力、ELISA检测细胞内PGE2浓度、流式细胞仪检测细胞周期变化、Western blotting检测细胞周期相关蛋白p21^(Wafl/cipl)和p27^(Kipl/pic2)的表达水平。结果:阿司匹林可抑制胰腺癌细胞生长并呈剂量依赖性减少细胞内PGE2的生成;阿司匹林可诱导细胞周期相关蛋白p21^(Wafl/cipl)和p27^(Kipl/pic2)表达升高并引起细胞阻滞在G0/G1期。但外源性PGE2并不能拮抗阿司匹林对细胞活力、细胞周期及细胞周期相关蛋白的影响。结论:阿司匹林抑制胰腺癌细胞的生长可能并非完全通过环氧合酶途径;诱导p21^(Wafl/cipl)和p27^(Kipl/pic2)表达的升高、进而诱导细胞周期的阻滞可能是其作用机制之一。

AIM： To observe the effects of aspirin and prostaglandin E2 （PGE2） on the cell viability and cell cycle in SW1990 human pancreatic carcinoma cell lines, and to investigate the mechanisms of aspirin- induced growth inhibition and cell cycle arrest. METHODS： After incubated with aspirin or PGE2 and their combination, the viability of SW1990 cells was measured by MTr assay. ＇Fne levels of intracellular PGE2 were determined by ELISA. ＇Fne effects of aspirin or PGE2 on cell cycle were investigated by flow cytometry （FCM）. The expression of p21^Wafl/cipl and p27^Kipl/pic2 the cyclin- dependent kinase inhibitors） were analyzed by Western blotting. RESYKTS： Aspirin could inhibit the growth of cells and level of intracellular PGE2 in a dose - dependent manner. Aspirin enhanced the expression of p21^Wafl/cipl and p27^Kipl/pic2 and induced cell cycle arrest at G0/G1 phase. PGE2 increased the cell viability of SW1990 cells. However, it couldn＇t antagonize the changes of cell viability and cell cycle that induced by aspirin. CONCLUSIONS： ＇Fne inhibitory effects of aspirin on growth and cell cycle of pancreatic carcinoma cells might not be mediated by a COX - dependent pathway completely. Cell cycle arrest induced by aspirin might be associated with up - regulation of p21^Wafl/cipl and p27^Kipl/pic2.