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Ectopic production of MDA-7/IL-24 inhibits invasion and migration of human lung cancer cells Ramesh R; Ito I; Gopalan B; Saito Y; Mhashilkar AM; Chada SMol Ther 2004[Apr]; 9 (4): 510-8We have previously observed the suppression of lung tumor growth in response to overexpression of melanoma differentiation-associated gene-7 (MDA-7)/interleukin-24 (IL-24; approved gene symbol IL24) in vitro and in vivo. MDA-7/IL-24 exerts its tumor-suppressive effects by multiple mechanisms, including the activation of the caspase cascade and the inhibition of angiogenesis. In this study, we used an adenoviral vector (Ad-mda7) to examine the effect of the ectopic production of MDA-7/IL-24 on cell migration and invasion by human non-small-cell lung carcinoma cells. Lung tumor cells (H1299 and A549) treated in vitro with Ad-mda7 migrated and invaded less than cells treated with phosphate-buffered saline (PBS) or Ad-Luc (vector control). MDA-7/IL-24 inhibited migration and invasion by down-regulating the production of phosphatidylinositol 3-kinase/protein kinase B, focal adhesion kinase, and matrix metalloproteinase-2 and -9 relative to PBS and Ad-Luc. Furthermore, tumor cells treated with Ad-mda7 ex vivo or with DOTAP:Chol-mda7 complex in vivo formed significantly fewer tumors in an experimental lung metastasis model. These results show that MDA-7/IL-24 inhibits invasion and migration by lung cancer cells by down-regulating proteins associated with these processes, resulting in reduced metastasis. Thus, Ad-mda7 should be considered a therapeutic agent that can inhibit primary tumor growth and prevent metastasis.|*Gene Transfer Techniques[MESH]|Adenoviridae/genetics[MESH]|Caspases/metabolism[MESH]|Cell Line, Tumor[MESH]|Cell Movement[MESH]|Cell Survival[MESH]|Down-Regulation[MESH]|Focal Adhesion Kinase 1[MESH]|Focal Adhesion Protein-Tyrosine Kinases[MESH]|Gelatin/chemistry[MESH]|Genes, Tumor Suppressor[MESH]|Genetic Therapy/methods[MESH]|Humans[MESH]|Immunoblotting[MESH]|Interleukins/*biosynthesis[MESH]|Luciferases/metabolism[MESH]|Lung Neoplasms/*metabolism/*pathology[MESH]|Matrix Metalloproteinase 2/metabolism[MESH]|Matrix Metalloproteinase 9/metabolism[MESH]|Neoplasm Invasiveness[MESH]|Neoplasm Metastasis/prevention & control[MESH]|Neovascularization, Pathologic[MESH]|Phosphatidylinositol 3-Kinases/metabolism[MESH]|Protein Serine-Threonine Kinases/metabolism[MESH]|Protein-Tyrosine Kinases/metabolism[MESH]|Proto-Oncogene Proteins c-akt[MESH]|Proto-Oncogene Proteins/metabolism[MESH]|Resting Phase, Cell Cycle[MESH]|Time Factors[MESH] |
