Radiation-inducible PTEN expression radiosensitises hepatocellular carcinoma cells

Int J Radiat Biol. 2010 Nov;86(11):964-74. doi: 10.3109/09553002.2010.496032. Epub 2010 Aug 2.

Abstract

Purpose: To test the radiosensitising effects of a tumour-suppressor gene, phosphatase and tensin homologue deleted from chromosome 10 (PTEN), in hepatocellular carcinoma cells (HCC).

Materials and methods: Radiation-induced wild-type PTEN or mutant PTEN was transfected into the SMMC-7721 human hepatocellular carcinoma cells. The expressions of PTEN and serine/threonine protein kinase (Akt) were detected by Western blot analysis. 3-(4,5)-dimethylthiahiazo-(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) absorbance and clonogenic survival assays were used to determine cell viability, proliferation and radiosensitivity. By performing cell-cycle analysis, terminal deoxynucleotidyltransferase (TdT)-mediated dUTP biotin nick end labelling (TUNEL) assays and gamma-histone H2A (γ-H2AX) formation assays, we were able to explore the mechanism of PTEN enhancement of radiosensitivity.

Results: Restoration of wild-type PTEN induced growth suppression and sensitised the cells to ionising radiation specifically by its lipid phosphatase activity through the PTEN-phosphatidylinositol 3-kinase (PI3K)-Akt signalling pathway. Restoring PTEN function correlated with G2/M arrest, apoptosis and the retardation of repair of radiation-induced double strand breaks (DSB).

Conclusions: Our study suggests that strategies designed to restore the expression of PTEN may represent promising new therapies for sensitising HCC cells to ionising radiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / radiation effects
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / radiotherapy*
  • Cell Line, Tumor
  • G2 Phase / radiation effects
  • Gene Expression / genetics
  • Gene Expression / physiology
  • Gene Expression / radiation effects*
  • Humans
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • PTEN Phosphohydrolase / radiation effects*
  • Phosphatidylinositol 3-Kinase / genetics
  • Phosphatidylinositol 3-Kinase / metabolism
  • Phosphatidylinositol 3-Kinase / radiation effects
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Protein-Serine-Threonine Kinases / radiation effects
  • Radiation Tolerance / genetics
  • Radiation Tolerance / physiology
  • Radiation Tolerance / radiation effects*
  • Time Factors
  • X-Rays / adverse effects*

Substances

  • Phosphatidylinositol 3-Kinase
  • Protein-Serine-Threonine Kinases
  • PTEN Phosphohydrolase
  • PTEN protein, human