Effects of SIRT2 on Growth and Lung Metastasis of Orthotopic Liver Cancer in Nude Mice and Its Mechanism

Abstract: The aim of this study was to investigate the effects of SIRT2 on growth and lung metastasis of orthotopic liver cancer in nude mice. SK-Hep-1 cells with stable knockdown of SIRT2 were screened with blasticidin and its knockdown efficiency was detected by qRT-PCR and Western blot. SIRT2-shRNA-SK-Hep-1 and shCont-SK-Hep-1 cells were respectively injected into the orthotopic liver of nude mice. The liver and lung tissues of nude mice were removed after 8 weeks of injection. The size of orthotopic liver cancer and the number of lung metastatic nodules were compared between the two groups. Next， the protein levels of SIRT2， p-AKT， AKT， p-GSK3β， GSK3β， active β-catenin and β-catenin in nude mice were detected by Western blot and immunohistochemistry. The results showed SK-Hep-1 cell lines with stable knockdown of SIRT2 were successfully established. Compared with shCont-SK-Hep-1 group， the volume of liver cancer in SIRT2-shRNA-SK-Hep-1 group was decreased (P<0.05) and the number of lung metastatic nodules in SIRT2-shRNA-SK-Hep-1 group was decreased significantly (P<0.05). Western blot showed that the protein levels of p-AKT， p-GSK3β， active β-catenin， β-catenin in the SIRT2 knockdown group were decreased， the protein level of GSK3β was increased， the protein level of AKT was no difference. Immunohistochemistry showed that the protein levels of p-AKT， p-GSK3β， β-catenin in the SIRT2 knockdown group was decreased. The results indicated that SIRT2 knockdown can inhibit the growth and lung metastasis of human hepatocarcinoma cells by activating AKT， subsequently influencing on GSK3β/β-catenin signaling pathway in orthotopic liver cancer of nude mice.

CSTR: 32200.14.cjcb.2018.03.0003