Effects of p16 gene on biological behaviours in hepatocellular carcinoma cells

World J Gastroenterol. 2003 Jan;9(1):84-8. doi: 10.3748/wjg.v9.i1.84.

Abstract

Aim: To investigate the effects of p16 gene on biological behaviours in hepatocellular carcinoma cells.

Methods: HCC cell lines SNU-449 and HepG2.2.15 were infected respectively by a replication defective, recombinant retrovirus capable of producing a high level of p16 protein expression (pCLXSN-p16). G418 resistant stable P16 protein expression cell lines were selected. And the biological behaviours of the p16 gene transfected HCC cells were observed.

Results: Initial in vitro experiments in HCC cell line SNU-449 with loss of p16 protein expression demonstrated the pCLXSN-p16 treatment significantly inhibited cell growth. But there was no treatment effect when the pCLXSN-p16 was used in another HCC cell line HepG2.2.15 which has positive p16 protein expression. Subsequent study in a nude mouse model demonstrated that the p16 gene transfected SNU-449 had a lower succeeding rate in the first time establishment of tumors and grew more slowly in the nude mice when compared with non-transfected SNU-449. Moreover, the nude mice inoculated with transfected SNU-449 had a longer surviving time than those inoculated with non-transfected SNU-449.

Conclusion: Our results show that the p16INK4a gene transfer can inhibit the proliferation and reduce the invasion ability of hepatocellular carcinoma.

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Cycle / physiology
  • Cell Division / physiology
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16 / therapeutic use
  • Genes, p16*
  • Genetic Therapy / methods
  • Humans
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Mice
  • Mice, Nude
  • Retroviridae / genetics
  • Retroviridae / metabolism
  • Survival Rate
  • Tumor Cells, Cultured

Substances

  • Cyclin-Dependent Kinase Inhibitor p16