Contribution of angiogenesis to the progression of colon cancer: Possible inhibitory effect of angiogenesis inhibitor TNP-470 on tumor growth and hepatic metastasis

Citation
S. Takatsuka et al., Contribution of angiogenesis to the progression of colon cancer: Possible inhibitory effect of angiogenesis inhibitor TNP-470 on tumor growth and hepatic metastasis, INT J ONCOL, 17(2), 2000, pp. 253-258
Citations number
21
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
INTERNATIONAL JOURNAL OF ONCOLOGY
ISSN journal
10196439 → ACNP
Volume
17
Issue
2
Year of publication
2000
Pages
253 - 258
Database
ISI
SICI code
1019-6439(200008)17:2<253:COATTP>2.0.ZU;2-N
Abstract
The contribution of angiogenesis to tumor growth and hepatic metastasis of colorectal cancer was investigated by means of immunohistochemical study an d in vitro and in vivo experiments. Colorectal cancer specimens from 30 pat ients with hepatic metastasis and 39 patients without hepatic metastasis we re studied by staining with antibodies against factor VIII-related antigen. Microvessel count in patients with liver metastasis was significantly high er than in those without liver metastasis (p<0.005). The effect of TNP-470 was evaluated with in vitro and in vivo experiments using human colon cance r cell line, LM and the highly hepatic metastasis cell line, LM-H5. The eff ect of TNP-470 on the proliferation of the cancer cells and human umbilical vein endothelial cells (HUVECs) was examined. TNP-470 inhibited more sensi tively the proliferation of HUVECs than cancer cells in vitro. IC50 was app roximately 3 pg/ml in HUVECs and approximately 2 mu g/ml in cancer cells. T he effect of TNP-470 on the growth of xenografts and liver metastases by LM -H5 in nude mice was examined. TNP-470 (30 mg/kg) was administered by subcu taneous injection every third day for 4 weeks. TNP-470 inhibited both the g rowth of xenograft and the hepatic metastasis. The number of metastatic foc i in the liver was 78.2+/-30.1 in the control group and 20.6+/-16.5 in the treated group. These results suggest that TNP-470 is a potent agent to inhi bit tumor growth and hepatic metastasis of colon cancer.