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.
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Acknowledgements
The authors thank Stacey Mott and Willie Virgil for technical assistance and Peggy James for the preparation of the manuscript. This work was supported in part by the Specialized Program of Research Excellence (SPORE) in Lung Cancer (P50-CA70907) (JA Roth), by Public Health Service grant P01CA78778-01A1 (JA Roth), by Cancer Center Support grant CA16672, NCI grant R43 CA86587 (S Chada), and by a sponsored research agreement with Introgen Therapeutics, Inc.
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Saeki, T., Mhashilkar, A., Swanson, X. et al. Inhibition of human lung cancer growth following adenovirus-mediated mda-7 gene expression in vivo. Oncogene 21, 4558–4566 (2002). https://doi.org/10.1038/sj.onc.1205553
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DOI: https://doi.org/10.1038/sj.onc.1205553
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