TNP-470 Suppresses the Tumorigenicity of HT1080 Fibrosarcoma TumorThrough the Inhibition of VEGF Secretion From the Tumor Cells

[摘要] Angiogenesis inhibitors are a novel class of promising therapeutic agents for treating cancer. TNP-470, a systemic analogueof fumagillin, is an angiogenesis inhibitor capable of suppressing the tumorigenicity in several animal models even thoughthe mechanisms of action have not been completely clarified. In the current study, we investigated the effects of TNP-470on human fibrosarcoma cellsin vivoandin vitro. The administration of TNP-470 could suppress the tumorigenicity ofHT1080 fibrosarcoma tumor. The conditioned medium from HT1080 fibrosarcoma cells treated with TNP-470 inhibitedthe proliferation and migration of human endothelial cell line, HUVEC and ECV304. The concentration of VEGF in theconditioned medium from HT1080 cells treated with TNP-470 was lower than that of the cells without TNP-470 treatment,indicating that TNP-470 downregulates the secretion of VEGF from HT1080 cells. These findings strongly suggest that thedirect action of TNP-470 on sarcoma cells inhibits angiogenesis through the downregulation of VEGF secretion and thisangiogenesis suppression resulted in the inhibition of tumorigenicity of HT1080 fibrosarcoma tumo.

[学科分类] 肿瘤学