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作 者:张晔[1] 曲秀娟[1] 刘云鹏[1] 荆薇[1] 杨向红[2] 侯科佐[1] 滕月娥[1] 张敬东[1]
机构地区:[1]中国医科大学附属第一医院肿瘤内科,辽宁沈阳110001 [2]中国医科大学附属盛京医院实验病理学研究室,辽宁沈阳110004
出 处:《中华肿瘤防治杂志》2009年第8期565-567,577,共4页Chinese Journal of Cancer Prevention and Treatment
基 金:国家自然科学基金(30770993);辽宁省科技攻关计划(2004225004-11)
摘 要: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.
关 键 词:胃肿瘤 组织芯片 AKT P-AKT 多药耐药相关蛋白质类
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