Inhibition of angiogenesis and HCT-116 xenograft tumor growth in mice by kallistatin

Abstract

To investigate the inhibitory effect of kallistatin (KAL) on angiogenesis and HCT-116 xenograft tumor growth. Heterotopic tumors were induced by subcutaneous injection of 2 multiply 10(6) HCT-11 cells in mice. Seven days later, 2 multiply 10(11) 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. Intratumor injection of rAAV-KAL inhibited tumor growth in the treatment group by 78% (171 +/- 52 mm(3)) at d 21 after virus infection compared to the control group (776 +/- 241 mm(3)). 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. 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.