Abstract
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
Substances
-
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