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General Research Article

Recombinant Adeno-associated Virus 9-mediated Expression of Kallistatin Suppresses Lung Tumor Growth in Mice

Author(s): Weihong Qu*, Jianguo Zhao, Yaqing Wu, Ruian Xu* and Shaowu Liu

Volume 21, Issue 1, 2021

Published on: 11 November, 2020

Page: [72 - 80] Pages: 9

DOI: 10.2174/1566523220999201111194257

Price: $65

Abstract

Background: Lung cancer remains the most common cause of cancer-related deaths in China and worldwide. Traditional surgery and chemotherapy do not offer an effective cure, although gene therapy may be a promising future alternative. Kallistatin (Kal) is an endogenous inhibitor of angiogenesis and tumorigenesis. Recombinant adeno-associated virus (rAAV) is considered the most promising vector for gene therapy of many diseases due to persistent and long-term transgenic expression.

Objective: The aim of this study was to investigate whether rAAV9-Kal inhibited NCI-H446 subcutaneous xenograft tumor growth in mice.

Methods: The subcutaneous xenograft mode was induced by subcutaneous injection of 2×107 H446 cells into the dorsal skin of BALB/c nude mice. The mice were administered with ssrAAV9-Kal (single- stranded rAAV9) or dsrAAV9-Kal (double-stranded rAAV9) by intraperitoneal injection (I.P.). Tumor microvessel density (MVD) was examined by anti-CD34 staining to evaluate tumor angiogenesis.

Results: Compared with the PBS (blank control) group, tumor growth in the high-dose ssrAAV9-Kal group was inhibited by 40% by day 49, and the MVD of tumor tissues was significantly decreased.

Conclusion: The results indicate that this therapeutic strategy is a promising approach for clinical cancer therapy and implicate rAAV9-Kal as a candidate for gene therapy of lung cancer.

Keywords: Recombinant adeno-associated virus, kallistatin, subcutaneous xenograft tumor growth, anti-angiogenic, lung cancer, gene therapy.

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