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

Journal of Experimental & Clinical Cancer Research

Xinyu Qin¹  Junxue Chen¹  Hongwei Zhang¹  Lai Wei²  Wei Zhu¹ 

[1] Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China;Department of cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China

关键词: Oncolytic adenovirus;    IL-24;    Breast cancer;   

Others  :  826371
DOI  :  10.1186/1756-9966-31-51

 received in 2012-02-06, accepted in 2012-04-06,  发布年份 2012

【 摘 要 】

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 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.

【 授权许可】

   
2012 Zhu et al.; licensee BioMed Central Ltd.

【 图 表 】

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