Inhibition of human lung cancer growth following adenovirus-mediated mda-7 gene expression in vivo.
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.
Saeki
Tomoyuki
T
Section of Thoracic Molecular Oncology, Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston 77030, USA.
Mhashilkar
Abner
A
Swanson
Xin
X
Zou-Yang
X Helena
XH
Sieger
Kerry
K
Kawabe
Shinichiro
S
Branch
Cynthia D
CD
Zumstein
Louis
L
Meyn
Raymond E
RE
Roth
Jack A
JA
Chada
Sunil
S
Ramesh
Rajagopal
R
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002454:Cell Differentiation; D002455:Cell Division; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D020287:In Situ Nick-End Labeling; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D009368:Neoplasm Transplantation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand; D013997:Time Factors; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099180:Interleukin-24
D051017:Apoptosis Regulatory Proteins; D007378:Interleukins; D008562:Membrane Glycoproteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha; D000099180:Interleukin-24; C105190:TNFRSF10A protein, human; C505653:TNFSF10 protein, human; C505654:Tnfsf10 protein, mouse