胃癌组织Akt和p-Akt蛋白及耐药相关蛋白表达临床意义的研究

Correlations between the expressions of Akt,p-Akt and P-gp,Gst-pi in gastric cancer

目的:检测胃癌组织Akt和p-Akt蛋白与胃癌生物学行为的相关性,及其与耐药相关蛋白P-gp和Gst-pi表达的相互关系。方法:将124例胃癌标本和16例正常胃黏膜标本制作成组织芯片,应用免疫组织化学SP法检测Akt、p-Akt、P-gp及Gst-pi蛋白的表达。同时利用蛋白质印迹法检测Akt、p-Akt、P-gp及Gst-pi在胃癌耐药细胞系SGC7901/ADR及其亲本细胞中的表达。结果:Akt和p-Akt在胃癌组织中的阳性表达率分别为82.3%和71.0%,显著高于正常胃黏膜,且两者表达均与胃癌的TNM分期有关(P<0.05)。p-Akt和P-gp表达成正相关,与Gst-pi表达无关,而Akt与P-gp、Gst-pi表达均无关。蛋白质印迹法结果提示,p-Akt在SGC7901/ADR中的表达显著高于其亲本细胞,而Akt在胃癌耐药和亲本细胞中的表达差异无统计学意义。结论:p-Akt过度表达可能参与P-gp介导的多药耐药,为临床采用Akt抑制剂以增加胃癌细胞的化疗敏感性提供了依据。

OBJECTIVE： To study the correlations between Akt,p-Akt expression levels and the biological behavior of gastric cancer, and explore the interrelations between expressions of Akt,p-Akt and P-gp,Gst-pi. METHODS： The expressions of Akt,p-Akt and P-gp,Gst-pi in gastric cancer （n= 124） and normal gastric mucosa （n=16） were detected by immunohistoehemical staining on tissue microarray sections. Western blot was employed to detect the expressions of Akt, p-Akt and P-gp, Gst-pi in SGC7901 and SGC7901/ADR cells. RESULTS： The expression levels of Akt （82.3%） and p-Akt （71.0%） in gastric cancer were higher than those in normal gastric mucosa （P〈0.05）. The expression levels of Akt and p-Akt were strongly correlated with the clinical stages （P〈0.05）. The expression of p-Akt,but not Akt, in gastric cancer had a positive correlation with that of P-gp. CONCLUSIONS： Multiple drug resistance in gastric cancer by P-gp mediated is strongly correlated with the expression of p Akt. Thus, it is of great importance to develop new compounds or strategies that are capable of circumventing P-gp mediated MDR with Akt interfering agents.