TNP-470 suppresses the tumorigenicity of HT1080 fibrosarcoma tumor through the inhibition of VEGF secretion from the tumor cells

Mitsunori Kaya, Takuro Wada, Satoshi Nagoya, Satoshi Kawaguchi, Toshihiko Yamashita, Nobuyuki Yamamoto, Mitsunori Yoshimoto, Futoshi Okada, Seiichi Ishii

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Angiogenesis inhibitors are a novel class of promising therapeutic agents for treating cancer. TNP-470, a systemic analogue of fumagillin, is an angiogenesis inhibitor capable of suppressing the tumorigenicity in several animal models even though the mechanisms of action have not been completely clarified. In the current study, we investigated the effects of TNP-470 on human fibrosarcoma cells in vivo and in vitro. The administration of TNP-470 could suppress the tumorigenicity of HT1080 fibrosarcoma tumor. The conditioned medium from HT1080 fibrosarcoma cells treated with TNP-470 inhibited the proliferation and migration of human endothelial cell line, HUVEC and ECV304. The concentration of VEGF in the conditioned 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 the direct action of TNP-470 on sarcoma cells inhibits angiogenesis through the downregulation of VEGF secretion and this angiogenesis suppression resulted in the inhibition of tumorigenicity of HT1080 fibrosarcoma tumor.

Original languageEnglish
Pages (from-to)197-202
Number of pages6
JournalSarcoma
Volume5
Issue number4
DOIs
Publication statusPublished - 2001
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging

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