Inhibition of human lung cancer growth following adenovirus-mediated mda-7 gene expression in vivo

Oncogene. 2002 Jul 4;21(29):4558-66. doi: 10.1038/sj.onc.1205553.


Overexpression of the melanoma differentiation associated gene-7 (mda-7) in vitro results in suppression of lung cancer cell proliferation. However, the ability of MDA-7 to suppress lung cancer in vivo has not been previously demonstrated. In this study, we investigated the possibility of inducing overexpression of the mda-7 gene in human non-small cell lung carcinoma cells in vivo and its effects on tumor growth. Adenovirus-mediated overexpression of MDA-7 in p53-wild-type A549 and p53-null H1299 subcutaneous tumors resulted in significant tumor growth inhibition through induction of apoptosis. In addition, decreased CD31/PECAM expression and upregulation of APO2/TRAIL were observed in tumors expressing MDA-7. In vivo studies correlated well with in vitro inhibition of lung tumor cell proliferation and endothelial cell differentiation mediated by Ad-mda7. These data demonstrate that Ad-mda7 functions as a multi-modality anti-cancer agent, possessing both, pro-apoptotic and anti-angiogenic properties. We demonstrate for the first time the potential therapeutic effects of Ad-mda7 in human lung cancer.

Publication types

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

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins
  • Cell Differentiation
  • Cell Division
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Genes, Tumor Suppressor
  • Humans
  • In Situ Nick-End Labeling
  • Interleukins / genetics*
  • Interleukins / metabolism*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Membrane Glycoproteins / metabolism
  • Mice
  • Neoplasm Transplantation
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor / metabolism
  • TNF-Related Apoptosis-Inducing Ligand
  • Time Factors
  • Transplantation, Heterologous
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / metabolism


  • Apoptosis Regulatory Proteins
  • Interleukins
  • Membrane Glycoproteins
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFRSF10A protein, human
  • TNFSF10 protein, human
  • Tnfsf10 protein, mouse
  • Tumor Necrosis Factor-alpha
  • interleukin-24