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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 detect the correlation between Akt and p-Akt protein and the biological behavior of gastric cancer and its relationship with the expression of P-gp and Gst-pi. Methods: 124 gastric cancer specimens and 16 normal gastric mucosa specimens were made into tissue microarrays. The expressions of Akt, p-Akt, P-gp and Gst-pi proteins were detected by immunohistochemical SP method. At the same time, the expression of Akt, p-Akt, P-gp and Gst-pi in gastric cancer cell line SGC7901 / ADR and their parental cells were detected by Western blot. Results: The positive rates of Akt and p-Akt in gastric cancer tissues were 82.3% and 71.0%, respectively, which were significantly higher than those in normal gastric mucosa (P <0.05). There was a positive correlation between p-Akt and P-gp expression but not Gst-pi expression, while Akt had no correlation with P-gp and Gst-pi expression. The result of Western blotting showed that the expression of p-Akt in SGC7901 / ADR was significantly higher than that of its parental cells, while there was no significant difference in the expression of Akt between drug-resistant and parental cells. CONCLUSION: Overexpression of p-Akt may be involved in the multidrug resistance mediated by P-gp, providing a basis for clinical use of Akt inhibitors to increase chemosensitivity of gastric cancer cells.