The effect of PTEN on proliferation and drug-, and radiosensitivity in malignant glioma cells

Anticancer Res. 2011 May;31(5):1653-8.

Abstract

Background: Deletions or mutations of the phosphatase and tensin homolog (PTEN) are frequently observed in malignant glioma and are responsible for progression of the disease. Since the molecule is a promising target for gene therapy, the effects of PTEN on glioma proliferation in combination with the anti-neoplastic agent, temozolomide, and ionizing radiation were investigated.

Materials and methods: An adenoviral vector encoding PTEN was used. After infection, changes in proliferation, the cell cycle, as well as drug- and radiosensitivity were investigated.

Results: Expression of PTEN led to a 1.21-fold prolongation of the doubling time of the cells. It reduced G(1) and increased G(2)/M populations. Forced PTEN expression conferred sensitivity to temozolomide and/or ionizing radiation.

Conclusion: In addition to counteracting cell proliferation, expression of PTEN presented advantages in the chemo- and radiosensitivity of glioma cells. Methods for up-regulation of PTEN may have a role in increasing the efficacy of current adjuvant therapies.

MeSH terms

  • Adenoviridae / genetics
  • Antineoplastic Agents, Alkylating / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Blotting, Western
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy*
  • Cell Cycle / drug effects
  • Cell Cycle / radiation effects
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • Combined Modality Therapy
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / pharmacology
  • Genetic Therapy
  • Glioma / pathology
  • Glioma / therapy*
  • Humans
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism*
  • Radiation Tolerance*
  • Radiation, Ionizing*
  • Temozolomide
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents, Alkylating
  • Dacarbazine
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Temozolomide