Fumagillin inhibits colorectal cancer growth and metastasis in mice: an in vivo and in vitro study of antiangiogenesis
- VernacularTitle:烟曲霉素抑制小鼠结直肠癌生长及转移的体内外研究
- Author:
Xiaonan CUI
;
Xinmiao LIANG
;
Li HOU
- Publication Type:Journal Article
- Keywords:
angiogenesis;
Fumagillin;
SCIDmouse;
coloncancer;
humanumbilicalvein endothelial cells
- From:China Oncology
2010;20(2):86-94
- CountryChina
- Language:Chinese
-
Abstract:
Background and purpose: Fumagillin is an inhibitor of type 2 methionine aminopeptidase that can block blood vessel formation. However, its molecular mechanism and therapeutic value in colon cancer still remain to be elucidated.ln this study, the effect of Fumagillin on the growth of colon cancer was examined. Methods: Twenty mice were divided into 4 groups and injected subcutaneously with 5×10~5/L WiDr or HT-29 cells in 200 μL phosphate-buffered saline (PBS) respectively. After 4 weeks, intraperitoneal injections of Fumagillin (0.1 mg/kg), Cyclo (1 mg/kg), or both were given every 2 days for 4 weeks. The tumor weight and microvessel density (MVD) were examined. Gene-expression profiles were examined by microarray analysis of human umbilical endothelial cells (HUVECs). Results: The Fumagillin-treated mice showed smaller tumor mass and lower MVD-CD105 levels than control ones. In vitro proliferation and tube formation of HUVEC was also significantly decreased by Fumagillin. Microarray analysis of Fumagillin-treated HUVECs showed up-regulation of 71 genes and down-regulation of 143 genes. Expression changes were involved in cell proliferation, migration, adhesion and gene transcription. Quantitative real time-polymerase chain reaction and Westem blot revealed decreased expression of cyclin E2, activated leukocyte cell adhesion molecule (ALCAM), and intercellular adhesion molecule-1 (ICAM-1) genes in the presence of Fumagillin. Conclusion: Fumagillin was found to suppress colorectal cancer growth by suppressing angiogenesis. The down-regulation of cyclin E2, ALCAM and ICAM-1 by fumagillin may be involved in the anti-angiogenesis.
