Article

Oncolytic adenovirus armed with IL-24 Inhibits the growth of breast cancer in vitro and in vivo.

Journal of Experimental & Clinical Cancer Research (impact factor: 2.15). 05/2012; 31(1):51. DOI:10.1186/1756-9966-31-51
Source: PubMed

ABSTRACT BACKGROUND: 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 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.

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Keywords

anti-tumor activity
 
breast cancer
 
breast tumor cells
 
cancer gene therapy strategy
 
fibroblasts
 
human breast cancer cell MDA-MB-231
 
level IL-24 expression
 
metastatic breast tumor
 
MTT assay
 
normal fibroblast cell MRC-5
 
nude mice
 
nude mice model
 
oncolytic adenovirus armed
 
orthotopic breast tumor growth
 
p<0.05 Mantal-Cox test
 
promising candidate
 
tail vein injection
 
ventricular injection
 
vivo anti-tumor effect
 
vivo luminescence imaging