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Oncolytic adenovirus co-expressing miRNA-34a and IL-24 induces superior antitumor activity in experimental tumor model

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Abstract

It has been demonstrated that numerous microRNAs (miRNAs) have potent tumor-suppressing effects on a variety of cancers, implicating a possible application of miRNA in tumor therapy. Oncolytic adenovirus is a suitable vector to deliver tumor suppressor genes for treatment of cancers. However, it remains unknown whether co-expression of tumor suppressor genes and miRNAs can contribute to a more potent antitumor capacity within an oncolytic adenovirus delivery system. In this study, we found that expression of miRNA-34a was reduced in hepatocellular carcinoma (HCC), and the reduced expression of miRNA-34a was associated with worse outcome of HCC patients. Thus, we developed an oncolytic adenoviral vector, AdCN205, to co-express miRNA-34a and IL-24 driven by an adenovirus endogenous E3 promoter in HCC cells. High levels of miRNA-34a and IL-24 expression were detected in AdCN205-IL-24-miR-34a-infected HCC cells. AdCN205-IL-24-miR-34a significantly induced dramatic antitumor activity, as compared with that induced by AdCN205-IL-24 or AdCN205-miR-34a alone. Transfer of miRNA-34a into HCC cells inhibited the expression of its target genes, Bcl-2 and SIRT1. Treatment of established xenograft HCC tumors with AdCN205-IL-24-miR-34a in a mouse model resulted in complete tumor regression without recurrence. Taken together, our data provide a promising and reasonable delivery strategy of double-aimed cancer therapy, in which miRNAs and tumor-suppressing genes are used simultaneously.

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Acknowledgments

This work was supported by funds from National Natural Sciences Foundation of China (30872984, 81020108026, and 81090423) and National Basic Research Program of China (973 Program, no. 2010CB529406).

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All authors have no potential conflicts of interest.

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Authors and Affiliations

  1. Lab. of Biotherapy of Cancer, Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China

    Wenjia Lou, Qing Chen, Leina Ma, Jia Liu, Zhi Yang, Junjie Shen, Youhong Cui, Xiu-wu Bian & Cheng Qian

  2. Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Zhejiang, Hangzhou, China

    Wenjia Lou

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  1. Wenjia Lou
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  2. Qing Chen
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Correspondence to Cheng Qian.

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Lou, W., Chen, Q., Ma, L. et al. Oncolytic adenovirus co-expressing miRNA-34a and IL-24 induces superior antitumor activity in experimental tumor model. J Mol Med 91, 715–725 (2013). https://doi.org/10.1007/s00109-012-0985-x

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  • DOI: https://doi.org/10.1007/s00109-012-0985-x

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