Induction of cytotoxicity by photoexcitation of TiO2 can prolong survival in glioma-bearing mice

Mol Biol Rep. 2011 Jan;38(1):523-30. doi: 10.1007/s11033-010-0136-9. Epub 2010 Mar 30.

Abstract

We have investigated the possibility that photoexcited titanium dioxide (TiO2) could inhibit the growth of malignant cells. We studied the anti-glioma effects of nano-TiO2 excited with ultraviolet A (UVA) irradiation both in vitro and in vivo. Transmission electron microscopy demonstrated that glioma cells take up TiO2 by phagocytosis, and vital staining revealed that TiO2 alone has no effect on glioma cell proliferation. However, if TiO2 was combined with UVA irradiation the proliferation rate was decreased significantly compared to controls (P<0.05). RT-PCR suggested that TiO2 induction of glioma cell apoptosis is associated with changes in the expression of genes encoding Bcl-2 family members. We then investigated the in vivo antitumor effects of combined TiO2 plus UVA treatment of established glioma tumors. TiO2 plus UVA led to pronounced areas of necrosis, elevated indices of apoptosis, delayed tumor growth, and increased survival compared with the TiO2-alone control group (P<0.001). Log-rank survival analysis showed that median survival duration was prolonged (P<0.001). These findings suggest that nano-TiO2 based photodynamic therapy has potential in the treatment of glioma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Cell Death / drug effects
  • Cell Death / radiation effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • Endocytosis / drug effects
  • Endocytosis / radiation effects
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Glioma / genetics
  • Glioma / pathology*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles / ultrastructure
  • Necrosis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Survival Analysis
  • Titanium / metabolism
  • Titanium / pharmacology*
  • Titanium / radiation effects*
  • Ultraviolet Rays*
  • Xenograft Model Antitumor Assays*

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • titanium dioxide
  • Titanium