Over-expression of Gadd45a enhances radiotherapy efficacy in human Tca8113 cell line

Acta Pharmacol Sin. 2011 Feb;32(2):253-8. doi: 10.1038/aps.2010.208.

Abstract

Aim: To investigate the effect of the growth arrest- and DNA damage-inducible Gadd45a gene on the radiosensitivity of human tongue squamous cell carcinoma cell line to ionizing radiation (IR).

Methods: Short interfering ribonucleic acid (si-RNA) targeting Gadd45a or an irrelevant mRNA (nonsense si-RNA) was chemically synthesized. The constructed si-RNAs were transfected into Tca8113 cells and Gadd45a expression was determined using quantitative real-time PCR and Western-blot. After 24-h exposure to IR at a dose rate of 4 Gy/min, apoptosis of Tca8113 cells was detected using flow cytometry, and radiosensitivity was measured using MTT assays.

Results: IR apparently increased the expression of Gadd45a at mRNA and protein levels in Tca8113 cells. The effect was efficiently inhibited by transfection with Gadd45a si-RNA (P<0.01). Furthermore, silencing Gadd45a gene significantly increased cell viability and decreased the percentage of apoptotic cells during irradiation, which indicated that IR-induced Gadd45a over-expression could increase the radiosensitivity of Tca8113 cells.

Conclusion: These results indicated that targeting Gadd45a may have important therapeutic implications in sensitizing Tca8113 cells to IR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Apoptosis / radiation effects
  • Blotting, Western
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / radiotherapy*
  • Cell Cycle Proteins / genetics*
  • Cell Line, Tumor
  • Cell Survival / genetics
  • Cell Survival / radiation effects
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing
  • Humans
  • Nuclear Proteins / genetics*
  • Polymerase Chain Reaction
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • Radiation, Ionizing
  • Tongue Neoplasms / genetics
  • Tongue Neoplasms / pathology
  • Tongue Neoplasms / radiotherapy*
  • Transfection

Substances

  • Cell Cycle Proteins
  • GADD45A protein, human
  • Nuclear Proteins
  • RNA, Messenger
  • RNA, Small Interfering