PI3K/AKT/mTOR信号通路在膀胱癌中的作用

The Role of PI3K/AKT/mTOR Signaling Pathway in Bladder Cancer

目的:分析磷脂酰肌醇3激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白(PI3K/AKT/mTOR)信号通路在膀胱癌中的作用。方法:选取60只SD健康雄性大鼠,采用随机数字法分为对照组、模型组和干预组,每组各20只。模型组和干预组大鼠以致癌物BBN灌胃8周建立膀胱癌模型,建模成功后,干预组大鼠注射PI3K抑制剂,连续干预6周。观察三组大鼠膀胱组织病理学变化,比较各组大鼠血清炎性因子指标、氧化应激指标、PI3K/AKT/mTOR信号通路蛋白表达和CK-19、CYFRA21-1水平的变化。结果:与对照组相比,模型组和干预组大鼠血清转化生长因子-β1(TGF-β1)、白细胞介素-1β(IL-1β)、C反应蛋白(CRP)、丙二醛、一氧化氮、PI3K、AKT、mTOR蛋白表达量、CK-19、CYFRA21-1水平升高,总抗氧化能力(T-AOC)、超氧化物歧化酶(SOD)水平降低(P<0.05)。与模型组相比,干预组血清TGF-β1、IL-1β、CRP、丙二醛、一氧化氮、PI3K、AKT、mTOR蛋白表达量、CK-19、CYFRA21-1水平均降低,T-AOC、SOD水平升高(P<0.05)。结论:PI3K抑制剂通过PI3K/AKT/mTOR信号通路遏制膀胱癌的发展。

Objective:To analyze the role of phosphatidylinositol 3 kinase/protein kinase B/mammalian rapamycin target(PI3K/AKT/mTOR)signaling pathway in bladder cancer.Method:A total of 60 healthy male SD rats were selected and divided into control group,simulation group and intervention group by random number method,with 20 rats in each group.Rats in the simulation group and intervention group were given the carcinogen BBN by gavage for 8 weeks to establish a bladder cancer model.The histopathological changes of the three groups of rats were observed,and the serum inflammatory factor indexes,oxidative stress indexes,PI3K/AKT/mTOR signaling pathway protein expression and the levels of CK-19 and CYFRA21-1 were compared among the three groups.Results:Compared with the control group,the levels of serum transforming growth factor(TGF-β1),interleukin-1β(IL-1β),C-reactive protein(CRP),malondialdehyde,nitric oxide,PI3K,AKT,mTOR protein expression,CK-19,CYFRA21-1 were increased in both the model group and the intervention group,while total antioxidant capacity(T-AOC)and superoxide dismutase(SOD)levels were decreased(P<0.05).Compared with the model group,TGF-β1,IL-1β,CRP,malondialdehyde,nitric oxide,PI3K,AKT,mTOR protein expression,CK-19,CYFRA21-1 levels were decreased in the intervention group,while T-AOC and SOD levels were increased(P<0.05).Conclusion:PI3Kinhibitors inhibit the development of bladder cancer through the PI3K/AKT/mTOR signaling pathway.