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

Mol Med. 2001 Apr;7(4):271-82.

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 anti-tumor 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Annexin A5 / metabolism
  • Blotting, Western
  • Cell Division / drug effects
  • Cell Line
  • Cell Separation
  • Chromosome Mapping
  • Chromosomes, Human, Pair 1
  • Coloring Agents / pharmacology
  • Dose-Response Relationship, Drug
  • Exons
  • Flow Cytometry
  • Genes, Tumor Suppressor / genetics
  • Genetic Therapy / methods*
  • Growth Substances / genetics*
  • Growth Substances / metabolism*
  • Humans
  • In Situ Nick-End Labeling
  • Interleukins*
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Neoplasms / therapy*
  • Oxazines*
  • Propidium / pharmacology
  • Thymidine / metabolism
  • Time Factors
  • Transduction, Genetic
  • Trypan Blue / pharmacology
  • Tumor Cells, Cultured
  • Xanthenes*

Substances

  • Annexin A5
  • Coloring Agents
  • Growth Substances
  • Interleukins
  • Oxazines
  • Xanthenes
  • interleukin-24
  • resazurin
  • Propidium
  • Trypan Blue
  • Thymidine