Effects of insulin-like growth factors-IR and -IIR antisense gene transfection on the biological behaviors of SMMC-7721 human hepatoma cells

J Gastroenterol Hepatol. 2003 Mar;18(3):296-301. doi: 10.1046/j.1440-1746.2003.02961.x.

Abstract

Background and aims: Insulin-like growth factors (IGFs) are closely related to hepatocellular carcinoma growth. The study aim was to investigate the effects of IGF-IR and IGF-IIR antisense gene transfection on the biological behaviors of SMMC-7721 human hepatoma cells.

Methods: 7721-IGF-IR-AS cells (human hepatoma SMMC-7721 cells transfected with IGF-IR antisense gene in our previous study) were transfected with a plasmid vector expressing IGF-IIR cDNA in the antisense orientation by DOTAP liposome.7721-IGF-R-AS cells were obtained by selection with G418 and hygromycin. Morphological changes of the cells were observed with optic and electron microscopes. In vitro growth of the 7721-IGF-R-AS cells was observed with a soft agar test, MTT test and with naked mice inoculation test in vivo.

Results: The following changes were found in the SMMC-7721 cells after being transfected with the IGF-IR and IGF-IIR antisense genes: (i) the degree of malignancy of the tumor cells as revealed by cell morphology was ameliorated; (ii) the growth capability of the tumor cells in soft agar and their tumorigenicity in naked mice were significantly depressed. However, in the control groups, the SMMC-7721 cells transfected both with IGF-IR and IGF-IIR sense cDNA and SMMC-7721 cells transfected without any external genes, had no such changes. However, the cell growth curves had no significant differences among these three groups.

Conclusion: IGF-IR and IGF-IIR antisense genes could significantly restrain the malignant behavior of human hepatoma cells and might be useful in investigating a potential route for hepatocellular carcinoma gene therapy.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinogenicity Tests
  • Carcinoma, Hepatocellular / genetics*
  • Cell Division / physiology
  • Cell Nucleus / ultrastructure
  • China
  • Cytoplasm / ultrastructure
  • DNA, Antisense / chemistry*
  • DNA, Antisense / genetics*
  • DNA, Antisense / metabolism
  • DNA, Neoplasm / genetics
  • Humans
  • Liver / cytology
  • Liver Neoplasms / genetics*
  • Mice
  • Microscopy, Electron, Scanning
  • Receptor, IGF Type 1 / genetics*
  • Receptor, IGF Type 1 / metabolism
  • Receptor, IGF Type 2 / genetics*
  • Receptor, IGF Type 2 / metabolism
  • Receptors, Somatomedin / genetics*
  • Receptors, Somatomedin / metabolism
  • Transfection*
  • Tumor Cells, Cultured / cytology
  • Tumor Cells, Cultured / metabolism
  • Tumor Stem Cell Assay

Substances

  • Biomarkers, Tumor
  • DNA, Antisense
  • DNA, Neoplasm
  • Receptor, IGF Type 2
  • Receptors, Somatomedin
  • Receptor, IGF Type 1