塞来昔布通过c-Myc及Akt/mTORC1信号通路延缓c-Myc诱导小鼠肝细胞癌的发展

Celecoxib delays development of hepatocellular carcinoma induced by c-Myc in mice through c-Myc and Akt/mTORC1 signaling pathway

目的探讨塞来昔布对c-Myc诱导小鼠肝细胞癌发展的作用及其机制。方法选取FVB/N小鼠,尾静脉高压注射c-Myc建立肝细胞癌模型,将小鼠分为4组(每组7只):正常组、模型组、塞来昔布低、高剂量组(150、300 mg·kg^-1)。给药干预6周后采集样本,测定小鼠体重和肝重,比较各组小鼠肝脏和肝脏指数差异;HE检测小鼠肝脏组织病变情况;IHC检测小鼠肝脏组织中Ki67蛋白表达情况;West-ern blot检测小鼠肝组织中c-Myc、p-Akt T308、p-Akt S473、p-4EBP1蛋白的表达水平。结果与正常组相比,模型组肝脏重量和肝重指数明显增大;肝脏组织多核、固缩现象明显;细胞核大量Ki67阳性染色;c-Myc和p-Akt T308、p-Akt S473、p-4EBP1蛋白表达明显增加。不同剂量塞来昔布干预后能明显抑制和改善上述指标的变化。结论塞来昔布可以通过调控c-Myc及Akt/mTORC1信号通路延缓c-Myc诱导小鼠肝细胞癌的发展。

Aim To investigate the effect of celecoxib on the development of c-Myc-induced hepatocellular carcinoma in mice and mechanism.Methods Hepa-tocellular carcinoma model was established by over-ex-pression of c-Myc in FVB/N mice by tail vein high-pressure transfection.The mice were divided into 4 groups:normal group,model group,celecoxib treatment group(150,300 mg·kg^-1)(n=7).After 6 weeks of drug administration,samples were collected and the body weight and liver weight of the mice were meas-ured.The differences in liver and liver index were compared by statistical methods.The liver tissue le-sions of mice were detected by HE staining and IHC staining.The expression of Ki67 protein was detected by IHC.The expression levels of c-Myc,p-Akt T308,p-Akt S473 and p-4EBP1 protein in mouse liver tissues were detected by Western blot.Results Compared with normal group,the liver weight and liver weight in-dex of model group increased significantly;the multin-uclear and pyknosis of liver tissues was obvious;the Ki67 positive staining of the nucleus appeared;c-Myc and p-Akt T308,p-Akt S473,p-4EBP1 protein expres- sion significantly increased. Different doses of celecox- ib could significantly inhibit and improve the changes of the above indicators. Conclusion Celecoxib can delay the development of c-Myc-induced hepatocellular carcinoma in mice by regulating c-Myc and Akt / mTORC1 signaling pathway.