Abstract
The present study was based on the unexpected discovery that norcantharidin exerted anti-angiogenesis activity when effects on growth of human colon cancer were studied. The aim was to further verify this finding and explore possible mechanisms using a tumor xenograft model in nude mice. We confirmed that norcantharidin (5 or 15 mg/kg) could inhibit angiogenesis of human colon cancer in vivo. In vitro, crossing river assay, cell adhesion assay and tube formation assay indicated that NCTD could reduce the migration, adhesion and vascular network tube formation ability of HUVECs. At the same time, the expression levels of VEGF and VEGFR-2 proteins which play important roles in angiogenesis were reduced as examined by western blotting analysis. Taken together, the results firstly showed NCTD could inhibit angiogenesis of human colon cancer in vivo, probably associated with effects on migration, adhesion and vascular network tube formation of HUVECs and expression levels of VEGF and VEGFR-2 proteins.
Highlights
Norcantharidin (NCTD) is a demethylated analogue of cantharidin which is an active ingredient of Chinese medicine-Mylabris
The results firstly showed NCTD could inhibit angiogenesis of human colon cancer in vivo, probably associated with effects on migration, adhesion and vascular network tube formation of human umbilical vein endothelial cells (HUVECs) and expression levels of VEGF and VEGFR-2 proteins
Our results proved that NCTD could inhibit angiogenesis of human colorectal cancer in vivo and vitro, which was associated with inhibition of proliferation, migration, adhesion and tube-formation
Summary
Norcantharidin (NCTD) is a demethylated analogue of cantharidin which is an active ingredient of Chinese medicine-Mylabris. It has been used as an anticancer drug for the treatment of colon cancer, primary hepatoma, carcinomas of esophagus and breast cancer, leukopenia in China for many years (Wang, 1989; Fang et al, 1993). Previous studies have shown that NCTD could suppress the invasion and metastasis of colorectal adenocarcinoma CT26 cells in vitro and in vivo models. There is an unexpected discovery that micro-vessels was less in the group treated with NCTD than the control group when we studied the effect of NCTD on HCT116 cell xenografts in nude mice. We suppose whether NCTD could inhibit angiogenesis of human colorectal cancer, which maybe a new mechanism for anticancer effect of NCTD
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