RESUMEN
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.
RESUMEN
Objective To investigate the effect of thermochemotherapy with 5 fluorocytosine(5 FC) on human colorectal carcinoma cell lines SW480 transfected with carcinoembryonic antigen (CEA) tissue specific cytosine deaminase (CD) in vitro.Methods Recombinant retroviral vector G1CEACDNa, in which CD gene was controlled under the CEA promoter, was introduced through liposome technique to the human colorectal carcinoma cell line SW480, and then the cells were selectively cultured in G418. The proliferated colonies were treated with the combined therapy of 5 FC and hyperthermia at a 43℃ over 30 min for 3 times. RT PCR was performed to analyze the expression of CD gene in target cells after thermochemotherapy. Results The CD gene expressed steadily in the target cells after 3 times of hyperthermic treatment. After the transfection of CD gene, SW480 CEACD cells were more sensitive to 5 FC than their parental cells (P