Melanoma differentiation associated gene-7 (mda-7): A novel anti-tumor gene for cancer gene therapy

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 anti-tumor effica cy 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. Al amar blue assay, and trypan-blue exclusion assay), apoptosis (TUNEL, and An nexin V staining visualized by fluorescent microscopy or FACs analysis), an d 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, RE, p16, ras, bar, and caspa se 3 in these cells. In addition, normal cell lines did not show inhibition of proliferation or apoptotic response to Ad-mda7. Moreover, Ad-mda7-trans duced 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.