Adenoviral-mediated mda-7 expression suppresses DNA repair capacity and radiosensitizes non-small-cell lung cancer cells

Oncogene. 2004 Sep 16;23(42):7125-31. doi: 10.1038/sj.onc.1207917.


The melanoma differentiation-associated gene-7 (mda-7) was identified by virtue of its enhanced expression in human melanoma cells induced into terminal differentiation. Enforced expression of mda-7 in human cancer cell lines of diverse origins results in the suppression of growth and induction of apoptosis. We have shown that adenoviral-mediated mda-7 (Ad-mda7) radiosensitizes non-small-cell lung cancer (NSCLC) cells by enhancing the apoptotic pathway. To identify the mechanism of this radiosensitization, we examined the level of proteins involved in the nonhomologous end-joining (NHEJ) pathway of DNA double-strand break (DSB) repair. Western blot analysis indicated that the expression of NHEJ pathway components Ku70, XRCC4, and DNA ligase IV was downregulated in NSCLC cells--A549 with Ad-mda7 treatment. No such change was observed in normal human CCD16 fibroblasts previously shown not to be radiosensitized by Ad-mda7. The biological significance of these changes of expression of proteins critical for repair of radiation-induced DSBs was confirmed via the analysis of DSB rejoining kinetics using pulsed field gel electrophoresis and assessment of host cell reactivation capacity following Ad-mda7 treatment. Based on these results, we hypothesize that Ad-mda7 sensitizes NSCLC cells to ionizing radiation by suppressing the activity of NHEJ, a pathway essential for repair of radiation-induced DSBs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / genetics*
  • Carcinoma, Non-Small-Cell Lung
  • Cell Line
  • Cell Line, Tumor
  • DNA Repair / genetics*
  • Genes, Tumor Suppressor
  • Glioma
  • Humans
  • Interleukins / genetics
  • Interleukins / metabolism*
  • Interleukins / radiation effects
  • Lung
  • Lung Neoplasms
  • Radiation, Ionizing
  • Radiation-Sensitizing Agents*
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / radiation effects
  • Transfection


  • Interleukins
  • Radiation-Sensitizing Agents
  • Recombinant Proteins
  • interleukin-24