Establishment of metastatic human hepatocellular carcinoma orthotopic transplantation model with palliative resection for investigating the biological characteristics of residual cancer in nude mice

Abstract

Objective To construct a metastatic human hepatocellular carcinoma (HCC) orthotopic transplantation model with palliative resection (PR) in nude mice for investigating the biological characteristics of the residual cancer,and to verify its efficacy.Methods A metastatic human HCC orthotopic nude mice model (MHCC97H) was established by using the method of bi-tumor inoculation in a single liver lobe.Two weeks after transplantation,the PR was applied to resect one tumor from the two.lobes.The tumor size was measured five weeks postresection.The flow cytometry was used to count the circulating tumor cells (CTCs) in peripheral blood.The fluorescence microscope and hematoxylin and eosin (HE)staining were adopted to determine the metastasis of the liver,lung,or abdomen.The Vimentin expression in brain or tumor tissues was detected by using immunohistochemical staining or Western blotting respectively.Results The incidence of bi-tumor formation,successful PR,and 5-week overall survival were 95.6％,95.3％,and 90.2％ respectively.The tumor size and CTCs in sham operation group,liver partial hepatectomy group,and PR group were increased in gradient; the incidence of intrahepatic metastasis was 15.4％,41.7％ and 83.3％ ; lung metastasis rate was 61.5％,91.7％ and 100.0％ ; and abdomen metastasis rate was 23.1％,50.0％ and 83.3％,respectively (P＜0.05).The Vimentin expression in brain or tumor tissues was up-regulated after surgical resection.Conclusion A metastatic human HCC orthotopic nude mice model combined with PR is successfully constructed,and it may be used to investigate the biological characteristics of the residual cancer. Key words: Carcinoma,hepatocellular; Palliative resection; Residual cancer; Model,nude mice