Title:Recombinant Adeno-associated Virus 9-mediated Expression of Kallistatin Suppresses Lung Tumor Growth in Mice
Volume: 21
Issue: 1
Author(s): Weihong Qu*, Jianguo Zhao, Yaqing Wu, Ruian Xu*Shaowu Liu
Affiliation:
- Department of School of Pharmacy & Life Science, Jiujiang University, Jiujiang, Jiangxi 332000,China
- School of Medicine and Institute of Molecular Medicine, Huaqiao University, Quanzhou, Fujian 361021,China
Keywords:
Recombinant adeno-associated virus, kallistatin, subcutaneous xenograft tumor growth, anti-angiogenic, lung
cancer, gene therapy.
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.
