8-氯腺苷抑制人胃癌细胞增殖相关信号蛋白的作用

目的探讨8-氯腺苷是否会影响肿瘤细胞的表皮生长因子受体(EGFR)及其相关信号蛋白的表达。方法人胃癌BGC-823细胞与不同浓度8-氯腺苷共孵育。SRB染色法观察细胞增殖;Western蛋白印迹法观察细胞增殖相关信号蛋白的表达。结果8-氯腺苷1.0,2.5,5.0,7.5和10μmol·L-1作用24h,浓度依赖性抑制BGC-823细胞增殖,抑制率分别为19.7%,31.8%,40.1%,49.8%和56.7%。7.5μmol·L-18-氯腺苷作用BGC-823细胞24,48和72h,抑制率分别为49.8%,49.1%和45.6%。Western蛋白印迹结果表明,8-氯腺苷2.5~7.5μmol·L-1作用24h,BGC-823细胞EGFR蛋白表达减少;Raf-1蛋白表达变化不显著;p-MEK和p-ERK磷酸化蛋白表达增加。结论8-氯腺苷可抑制BGC-823细胞增殖;改变EGFR-Raf/MEK/ERK等一系列信号蛋白的表达可能是其抑制细胞增殖的重要途径之一。

Effect of 8-chloroadenosine on proliferation related signal proteins in gastric carcinoma cells

AIM To study whether 8-chloroadenosine can influence the expression of epidermal growth factor receptor(EGFR) and related signal proteins. METHODS In vitro, BGC-823 cells were incubated with different concentrations of 8-chloroadenosine. The growth inhibition was evaluated with sulforhodamine B assays. Western-blot analysis was used to determine expression of signal transduction related proteins in BGC-823 cells. RESULTS After 24 h incubation, 8-chloroadenosine 1.0, 2.5, 5.0, 7.5 and 10 μmol·L^-1 concentration-dependently inhibited the growth of BGC-823 cells by 19.7%, 31.8%, 40.1%, 49.8% and 56.7%. When incubated with 8-chloroadenosine 7.5 μmol·L^-1 for 24, 48 and 72 h, growth of BGC-823 cells was inhibited by 49.8%, 49.1% and 45.6%, respectively. 8-Chloroadenosine 2.5－7.5 μmol·L^-1, 24 h, caused a concentration-dependent decrement on EGFR, and increment on p-MEK and p-ERK protein expression. The decrement of Raf-1 protein expression was not very remarkable. CONCLUSION 8-Chloroadenosine inhibits proliferation of cancer cells, which may be related to changing EGFR-Raf/MEK/ERK cascade.