阿司匹林对西罗莫司抗胃癌MKN45细胞体外增殖作用的影响研究

目的：研究阿司匹林对西罗莫司抗胃癌MKN45细胞体外增殖作用的影响及作用机制。方法：体外培养胃癌MKN45细胞,给予西罗莫司（0、0.5、1.0、2.0nmol·L-1）、阿司匹林（10mmol·L-1）＋西罗莫司（0、0.5、1.0、2.0nmol·L-1）,以MTT法测定并计算细胞增殖抑制率;通过实时定量聚合酶链式反应（PCR）测定正常胃上皮GES-1细胞、MKN45细胞和经西罗莫司（2.0nmol·L-1）、阿司匹林、阿司匹林＋西罗莫司（2.0nmol·L-1）处理后的MKN45细胞中环氧化酶2（COX-2）、白细胞介素1α（IL-1α）表达情况。结果：西罗莫司可抑制MKN45细胞增殖,且呈剂量依赖性;与西罗莫司比较,阿司匹林＋西罗莫司处理后的MKN45细胞增殖抑制率明显增加（P〈0.01）。mRNA相对表达量COX-2MKN45/GES-1、IL-1αMKN45/GES-1分别为1.49±0.17、1.58±0.19。与对照MKN45细胞比较,COX-2、IL-1α在经西罗莫司、阿司匹林、阿司匹林＋西罗莫司处理后的MKN45细胞中的表达均明显降低（P〈0.01）,其中组间均有统计学差异（P〈0.05或P〈0.01）。结论：阿司匹林可协同增强西罗莫司抑制胃癌MKN45细胞增殖的作用,其作用机制可能与抑制COX-2、IL-1α表达有关。

Effects of Aspirin on the Inhibitory Effects of Sirolimus against Proliferation of Gastric Cancer MKN45 Cells in Vitro

OBJECTIVE：To investigate the effect of aspirin on the inhibitory effects of sirolimus against proliferation of gastric cancer MKN45 cells in vitro,and to elucidate its possible mechanism.METHODS：Gastric cancer MKN45 cells were treated with sirolimus（0,0.5,1.0,2.0 nmol·L-1）or aspirin（10 mmol·L-1）combined with sirolimus（0,0.5,1.0,2.0 nmol·L-1）in vitro.MTT assay was used to detect the growth inhibitory rate of MKN45 cells.The real-time PCR was performed to examine the expression of cycloxyenase-2（COX-2） and interleukin-1 α（IL-1 α） in normal gastric epithelial cell GES-1,normal MKN45 cells and MKN45 cells treated with sirolimus（2.0 nmol·L-1）,aspirin alone and two drugs combination.RESULTS：The proliferation of MKN45 cells were inhibited by sirolimus in dosage-dependant manner.Compared with sirolimus alone,inhibition rate of aspirin combined with sirolimus on MKN45 cells was increased significantly（P0.01）.mRNA expression of COX-2 MKN45/GES-1 、IL-1α MKN45/GES-1 were 1.49±0.17 and 1.58±0.19.Compared with MKN45 cells in control group,the expression of COX-2 and IL-1α in treated MKN45 cells were decreased significantly（P0.01）,there was statistical difference among groups（P0.05 or P0.01）.CONCLUSIONS：The combination treatment of aspirin and sirolimus improve the sensitivity of gastric cancer MKN45 cells to sirolimus;the mechanism perhaps lies in the combination of the two drugs to inhibit the expression of COX-2 and IL-1α.