Abstract
Background
The mda-7 gene (melanoma differentiation associated gene-7) is a novel tumor suppressor gene. The anti-proliferative activity of MDA-7 has been previously reported. In this report, we analyze the antitumor efficacy of Ad-mda7 in a broad spectrum of cancer lines.
Materials and Methods
Ad-mda7-transduced cancer or normal cell lines were assayed for cell proliferation (tritiated thymidine incorporation assay, Alamar blue assay, and trypan-blue exclusion assay), apoptosis (TUNEL, and Annexin V staining visualized by fluorescent microscopy or FACs analysis), and cell cycle regulation (Propidium Iodide staining and FACs analysis).
Results
Ad-mda7 treatment of tumor cells resulted in growth inhibition and apoptosis in a temporal and dose-dependent manner. The anti-tumor effects were independent of the genomic status of p53, RB, p16, ras, bax, and caspase 3 in these cells. In addition, normal cell lines did not show inhibition of proliferation or apoptotic response to Ad-mda7. Moreover, Ad-mda7-transduced cancer cells secreted a soluble form of MDA-7 protein. Thus, Ad-mda7 may represent a novel gene-therapeutic agent for the treatment of a variety of cancers.
Conclusions
The potent and selective killing activity of Ad-mda7 in cancer cells but not in normal cells makes this vector a potential candidate for cancer gene therapy.
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Acknowledgements
This research was supported by Introgen Therapeutics Inc., Houston, TX. and NCI grant R43 CA86587 to SC.
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Contributed by A. B. Pardee.
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Mhashilkar, A.M., Schrock, R.D., Hindi, M. et al. Melanoma Differentiation Associated Gene-7 (mda-7): A Novel Anti-Tumor Gene for Cancer Gene Therapy. Mol Med 7, 271–282 (2001). https://doi.org/10.1007/BF03401847
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DOI: https://doi.org/10.1007/BF03401847