Bradykinin promotes vascular endothelial growth factor expression and increases angiogenesis in human prostate cancer cells

Hsin Shan Yu, Shih Wei Wang, An Chen Chang, Huai Ching Tai, Hung I. Yeh, Yu Min Lin, Chih Hsin Tang

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40 引文 斯高帕斯(Scopus)

摘要

Prostate cancer is the most commonly diagnosed malignancy in men and shows a tendency for metastasis to distant organs. Angiogenesis is required for metastasis. Bradykinin (BK) is an inflammatory mediator involved in tumor growth and metastasis, but its role in vascular endothelial growth factor (VEGF) expression and angiogenesis in human prostate cancer remains unknown. The aim of this study was to examine whether BK promotes prostate cancer angiogenesis via VEGF expression. We found that exogenous BK increased VEGF expression in prostate cancer cells and further promoted tube formation in endothelial progenitor cells and human umbilical vein endothelial cells. Pretreatment of prostate cancer with B2 receptor antagonist or small interfering RNA (siRNA) reduced BK-mediated VEGF production. The Akt and mammalian target of rapamycin (mTOR) pathways were activated after BK treatment, and BK-induced VEGF expression was abolished by the specific inhibitor and siRNA of the Akt and mTOR cascades. BK also promoted nuclear factor-κB (NF-κB) and activator protein 1 (AP-1) activity. Importantly, BK knockdown reduced VEGF expression and abolished prostate cancer cell conditional medium-mediated angiogenesis. Taken together, these results indicate that BK operates through the B2 receptor, Akt, and mTOR, which in turn activate NF-κB and AP-1, activating VEGF expression and contributing to angiogenesis in human prostate cancer cells.
原文英語
頁(從 - 到)243-253
頁數11
期刊Biochemical Pharmacology
87
發行號2
DOIs
出版狀態已發佈 - 1月 15 2014
對外發佈

ASJC Scopus subject areas

  • 生物化學
  • 藥理

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