Inhibition of autocrine IGF-II on effect of human HepG2 cell proliferation and angiogenesis factor expression

Tumour Biol. 2012 Oct;33(5):1767-76. doi: 10.1007/s13277-012-0436-x. Epub 2012 Jun 10.


Abnormal expression of insulin-like growth factor II (IGF-II) is associated with the hepatocyte malignant transformation and hepatocellular carcinoma (HCC) progress. In this study, specific IGF-II miRNA plasmids were constructed and transfected to HepG2 cells to knockdown IGF-II expression for observing effects on the cell proliferation, survival, apoptosis, angiogenesis, and anchorage-independent colony formation. IGF-II mRNA was evaluated by quantitative real-time polymerase chain reaction, and the level of IGF-II or vascular endothelial growth factor (VEGF) was quantitatively analyzed by ELISA. Our data shown that downregulation of IGF-II expression resulted in the viability alteration, proliferation inhibition, and apoptosis occurrence of HepG2 cells. The level of VEGF expression in the supernatant of HepG2 cells in the IGF-II-miRNA-transfected group was significantly decreasing (P < 0.01) than those in the untransfected group or the miRNA-neg-transfected group, with the susceptibility to anoikis and decreasing of anchorage-independent colony formation of HepG2 cells. Thus, we conclude that IGF-II is a potential molecular target for HCC gene therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Autocrine Communication / genetics*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Cell Proliferation
  • Cell Survival / genetics
  • Gene Expression Regulation, Neoplastic
  • Hep G2 Cells
  • Humans
  • Insulin-Like Growth Factor II / genetics*
  • Insulin-Like Growth Factor II / metabolism
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Neovascularization, Pathologic / genetics*
  • Neovascularization, Pathologic / metabolism
  • RNA Interference
  • Vascular Endothelial Growth Factor A / genetics


  • Vascular Endothelial Growth Factor A
  • Insulin-Like Growth Factor II