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

AIM： TO investigate the inhibitory effect of kallistatin （KAL） on angiogenesis and HCT-116 xenograft tumor growth.METHODS： Heterotopic subcutaneous injection of 2 Seven days later, 2 x 1011 injected intratumorally （n tumors were induced by x 106 HCT-11 cells in mice. rAAV-GFP or rAAV-KAL was = 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 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.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.