Molecular mechanism of the inhibitory effect of KS-5 on bFGF-induced angiogenesis in vitro and in vivo

Chieh Yu Peng, Shiow Lin Pan, Kuo Hsiung Lee, Kenneth F. Bastow, Che Ming Teng

研究成果: 雜誌貢獻文章同行評審

10 引文 斯高帕斯(Scopus)

摘要

Inhibition of angiogenesis controls the expansion and metastasis of many solid tumors and other related-diseases. KS-5 (1,7-dihydroxy-3-methoxyacridone), is an inactive analogue of the substituted 1-hydroxy acridone antiviral class. This study aimed at studying the effects of KS-5 on bFGF-induced angiogenesis in cultured human umbilical vein endothelial cells (HUVECs) in vitro and in vivo. KS-5 inhibited bFGF (10 ng/ml)-induced cell proliferation in a concentration-dependent manner, but did not exhibit significant cytotoxic effect examined by LDH release assay. KS-5 inhibited bFGF-induced angiogenesis was associated with decreasing DNA synthesis as evaluated by BrdU incorporation assay, and abrogating endothelial cell ERK1/2 and Akt protein phosphorylation, the major signaling pathways involved in cellular processes of angiogenesis. In addition, KS-5 also inhibited bFGF-induced phosphorylation of mTOR and the major downstream effectors, eIF4E and p70S6K. Moreover, bFGF-induced protein synthesis was also inhibited by KS-5. Most importantly, KS-5 treatment in nude mice inhibited in vivo angiogenesis as revealed by Matrigel implant assay. In conclusion, the present study suggests that KS-5 has potential anti-angiogenetic effect for cancer therapy and other angiogenesis-dependent diseases.
原文英語
頁(從 - 到)114-121
頁數8
期刊Cancer Letters
263
發行號1
DOIs
出版狀態已發佈 - 五月 8 2008
對外發佈

ASJC Scopus subject areas

  • 腫瘤科
  • 癌症研究

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