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


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.


CONCLUSIONS
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.
Diao
Yong
Y
Institute of Molecular Medicine, Huaqiao University, Quanzhou, Fujian Province, China. diaoyong@hqu.edu.cn
Ma
Jian
J
Xiao
Wei-Dong
WD
Luo
Jia
J
Li
Xin-Yan
XY
Chu
Kin-Wah
KW
Fung
Peter  W C
P
Habib
Nagy
N
Farzaneh
Farzin
F
Xu
Rui-An
RA
D020533:Angiogenesis Inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D000229:Dependovirus / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D045325:HCT116 Cells; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000378:metabolism / Q000628:therapy; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D018952:Antigens, CD34; D019394:Ki-67 Antigen; D015843:Serpins; C051324:kallistatin