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http://dx.doi.org/10.7314/APJCP.2012.13.4.1471

Treatment of Malignant Melanoma by Downregulation of XIAP and Overexpression of TRAIL with a Conditionally Replicating Oncolytic Adenovirus  

Li, Xin-Qiu (Department of Thyroid and Mammary Gland, Renmin Hospital, Hubei University of Medicine)
Ke, Xian-Zhu (Department of Thyroid and Mammary Gland, Renmin Hospital, Hubei University of Medicine)
Wang, Yu-Ming (Department of Thyroid and Mammary Gland, Renmin Hospital, Hubei University of Medicine)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.13, no.4, 2012 , pp. 1471-1476 More about this Journal
Abstract
Background and Aim: Currently available systemic therapies for malignant melanoma produce low response rates in patients, and more effective treatment modalities are clearly needed. The tumor necrosis factor (TNF)-related apoptosis-inducing ligand has a significant impact on therapy for patients with X-linked inhibitor of apoptosis protein-downregulation malignant melanoma. The primary objective of this study was to assess its therapeutic potential. Materials and Methods: We employed a conditionally replicating oncolytic adenoviral vector, named CRAd5.TRAIL/siXIAP, with the characteristics of over-expression of the therapeutic gene TRAIL and downregulation of XIAP in one vector. B16F10-luc cells were employed to detect anti-tumor activity of CRAd5.TRAIL/siXIAP in vitro and in vivo. Results: CRAd5.TRAIL/siXIAP enhanced caspase-8 activation and caspase-3 maturation in B16F10 cells in vitro. Furthermore, it more effectively infected and killed melanoma cells in vitro and in vivo than other adenoviruses. Conclusion: Taken together, the combination of upregulation of TRAIL and downregulation of siXIAP with one oncolytic adenoviral vector holds promise for development of an effective therapy for melanomas and other common cancers.
Keywords
Malignant melanoma; TNF-related apoptosis-inducing ligand; conditionally replicating oncolytic adenovirus;
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