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lüll Oncolytic adenovirus armed with IL-24 inhibits the growth of breast cancer in vitro and in vivo Zhu W; Wei L; Zhang H; Chen J; Qin XJ Exp Clin Cancer Res 2012[May]; 31 (1): 51BACKGROUND: Interleukin-24 (IL-24) is a cytokine that belongs to the IL-10 family. It can selectively induce cancer cell apoptosis which has been utilized as a cancer gene therapy strategy. METHODS: A recombinant type five adenovirus containing IL-24 gene (designated CNHK600-IL24) was constructed, whose replication is activated only in tumor cells. The replication of CNHK600-IL24 in breast tumor cells and fibroblasts were assessed by TCID50 and MTT assay; the secretion of IL-24 was measured by ELISA and western blotting. The in vivo anti-tumor effect of CNHK600-IL24 was investigated in nude mice carrying orthotopic or metastatic breast tumor. RESULTS: We observed that CNHK600-IL24 could replicate efficiently and resulted in high level IL-24 expression and massive cell death in human breast cancer cell MDA-MB-231 but not in normal fibroblast cell MRC-5. In addition, orthotopic breast tumor growth in the nude mice model was significantly suppressed when CNHK600-IL24 was administered. In the metastatic model generated by tail vein injection, CNHK600-IL24 virotherapy significantly improved survival compared with the same virus expressing EGFP (median survival CNHK600-IL24, 55 days vs. CNHK600-EGFP, 41 day, p < 0.05 Mantal-Cox test). A similar phenomenon was observed in the metastatic model achieved by left ventricular injection as suggested by in vivo luminescence imaging of tumor growth. CONCLUSION: The oncolytic adenovirus armed with IL-24, which exhibited enhanced anti-tumor activity and improved survival, is a promising candidate for virotherapy of breast cancer.|*Breast Neoplasms/genetics/metabolism[MESH]|*Interleukins/administration & dosage/genetics/metabolism[MESH]|*Oncolytic Virotherapy[MESH]|*Recombinant Proteins/administration & dosage/genetics/metabolism[MESH]|Adenoviridae[MESH]|Animals[MESH]|Apoptosis/genetics[MESH]|Cell Proliferation[MESH]|Female[MESH]|Genetic Vectors[MESH]|Humans[MESH]|Mice[MESH]|Mice, Nude[MESH]|Oncolytic Viruses/*genetics[MESH]|Xenograft Model Antitumor Assays[MESH] |