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World J Gastroenterol. Sep 14, 2007; 13(34): 4615-4619
Published online Sep 14, 2007. doi: 10.3748/wjg.v13.i34.4615
Inhibition of angiogenesis and HCT-116 xenograft tumor growth in mice by kallistatin
Yong Diao, Jian Ma, Wei-Dong Xiao, Jia Luo, Xin-Yan Li, Kin-Wah Chu, Peter WC Fung, Nagy Habib, Farzin Farzaneh, Rui-An Xu
Yong Diao, Xin-Yan Li, Rui-An Xu, Molecular Medicine Engineering Research Center of the Ministry of Education, Institute of Molecular Medicine, Huaqiao University, Quanzhou 362021, Fujian Province, China
Jian Ma, Kin-Wah Chu, Peter WC Fung, Department of Medicine, Hong Kong University, Hong Kong, China
Wei-Dong Xiao, Department of Pediatrics, University of Pennsylvania, United States
Jia Luo, Department of Pharmacy, Chicago University, United States
Nagy Habib, Department of Transplantation, Imperial College London, United Kingdom
Farzin Farzaneh, Department of Haematological & Molecular Medicine, King’s College London, London SE5 9NU, United Kingdom
Author contributions: All authors contributed equally to the work.
Supported by Hong Kong University Foundation (special donation from Madame Cho So Man) and Huaqiao University Foundation B105
Correspondence to: Professor Yong Diao, Institute of Molecular Medicine, Huaqiao University, Quanzhou 362021, Fujian Province, China. diaoyong@hqu.edu.cn
Telephone: +86-595-22690952 Fax: +86-595-22690952
Received: May 9, 2007
Revised: June 22, 2007
Accepted: June 25, 2007
Published online: September 14, 2007
Abstract

AIM: To investigate the inhibitory effect of kallistatin (KAL) on angiogenesis and HCT-116 xenograft tumor growth.

METHODS: Heterotopic tumors were induced by subcutaneous injection of 2 × 106 HCT-11 cells in mice. Seven days later, 2 × 1011 rAAV-GFP or rAAV-KAL was injected intratumorally (n = 5 for each group). The mice were sacrificed at d 28, by which time the tumors in the rAAV-GFP group had grown to beyond 5% of the total body weight. Tumor growth was measured by calipers in two dimensions. Tumor angiogenesis was determined with tumor microvessel density (MVD) by immunohistology. Tumor cell proliferation was assessed by Ki-67 staining.

RESULTS: Intratumor injection of rAAV-KAL inhibited tumor growth in the treatment group by 78% (171 ± 52 mm3) at d 21 after virus infection compared to the control group (776 ± 241 mm3). Microvessel density was significantly inhibited in tumor tissues treated with rAAV-KAL. rAAV-KAL also decreased the proportion of proliferating cells (Ki-67 positive cells) in tumors compared with the control group.

CONCLUSION: rAAV-mediated expression of KAL inhibits the growth of colon cancer by reducing angiogenesis and proliferation of tumor cells, and may provide a promising anti-angiogenesis-based approach to the treatment of metastatic colorectal cancer.

Keywords: Kallistatin, Adeno-associated virus, Angiogenesis inhibitors, Colon, Neoplasm