非甾体消炎药抑制小鼠胃癌转移潜能的研究

Inhibitory Effects of Nonsteroidal Antiinflammatory Drugs on the Metastatic Potential of Mice Gastric Cancer

目的:观察非甾体消炎药(nonsteroidal antiinflammatory drugs,NSAIDs)抑制小鼠胃癌转移潜能的效应,探讨其作用机制。方法:建立人胃癌细胞SGC7901裸鼠种植瘤模型,将30只小鼠随机分为3组:对照组、观察1组、观察2组,每组10只。对照组给予阿拉伯树胶,观察1组给予舒林酸,观察2组给予塞来昔布。采用免疫组化两步法和Western Blot检测CD44v6、ICAM-1、E-cadherin、FGF-1和VEGF的蛋白表达水平,用RT-PCR检测VEGF的mRNA水平。结果:观察1、2组CD44v6、ICAM-1、FGF-1和VEGF蛋白表达水平均明显低于对照组(P均<0.05),观察1、2组E-cadherin蛋白表达水平与对照组之间差异无统计学意义(P>0.05)。观察1、2组和对照组VEGF的mRNA水平分别为(30.9±14.4)%、(25.6±16.2)%、(46.5±28.7)%,观察1、2组VEGF的mRNA水平均明显低于对照组(P均<0.05)。结论:NSAIDs在体内具有显著抗胃癌效应,并可能通过调节某些肿瘤转移相关因子表达来抑制胃癌转移。

Objective： To observe the inhibitory effects in vivo of nonsteroidal antiinflammatory drugs（NSAIDs） on the metastatic potential of gastric cancer in mice, further to investigate their mechanisms. Methods： Thirty athymic mice＇s xenograft models with human gastric cancer cell SGC7901 were established and divided randomly into three groups：control,observation 1 and 2 groups with 10 mice in each group. The Arab sup,sulindac and celecoxib were orally administered to mice of control group,observation 1 and 2 groups,respectively. Immunohistochemistry of two step and Western Blot assays were applied to detect the protein expression of CD44v6,ICAM-1, E-cadherin, FGF-1 and VEGF. And RT-PCR technique was used to evaluate the mRNA level of VEGF. Results：The protein expression level of CD44v6, ICAM-1, FGF-1 and VEGF of both observation 1 and 2 groups were significantly lower than that of control group（P〈0.05）,but the expression of E-cadherin showed no significant difference among three groups. The mRNA levels of VEGF were （30. 9±14.4）% in observation 1 group,（25.6±16. 2）% in observation 2 group and （46.5 ± 28.7） % in control group. The mRNA levels of VEGF of observation 1 and 2 group were both obviously lower than that of control group（P〈0.05）. Conclusion： The NSAIDs had obvious anti-cancer effects in vivo against and might inhibit the metastasis of gastric cancer via regulating the expression of certain neoplasm metastasis-associated factors.