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