¹Section of Thoracic Molecular Oncology, Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, TX 77030, USA

²Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, TX 77030, USA

³Introgen Therapeutics Inc., Houston, Texas, TX 77030, USA

Correspondence to: R Ramesh, Department of Thoracic and Cardiovascular Surgery, Box 45, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas, TX 77030, USA; E-mail: rramesh@mdanderson.org

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.

Oncogene (2002) 21, 4558-4566 doi:10.1038/sj.onc.1205553

MDA-7; TRAIL; CD31; apoptosis; gene therapy; antiangiogenesis