Bradykinin promotes vascular endothelial growth factor expression and increases angiogenesis in human prostate cancer cells
Resource
Biochem. Pharmacol., 87(2), 243-253
Journal
Biochemical Pharmacology
Journal Volume
87
Journal Issue
2
Pages
243-253
Date Issued
2014
Author(s)
Yu, Hsin-Shan
Yu, Hsin-Shan
Wang, Shih-Wei
Wang, Shih-Wei
Chang, An-Chen
Yeh, Hung-I
Lin, Yu-Min
Lin, Yu-Min
Tang, Chih-Hsin
Abstract
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. ? 2013 Elsevier Inc.
Subjects
Angiogenesis; Bradykinin; Prostate cancer; VEGF
SDGs
Other Subjects
bradykinin; immunoglobulin enhancer binding protein; mammalian target of rapamycin; protein kinase B; small interfering RNA; transcription factor AP 1; vasculotropin; angiogenesis; article; cancer cell; carcinogenesis; cell function; cell invasion; cell migration; controlled study; endothelial progenitor cell; enzyme phosphorylation; human; human cell; male; metastasis; priority journal; promoter region; prostate cancer; protein expression; umbilical vein endothelial cell; upregulation; Angiogenesis; Bradykinin; Prostate cancer; VEGF; Bradykinin; Cells, Cultured; Gene Expression Regulation, Neoplastic; Human Umbilical Vein Endothelial Cells; Humans; Male; Neovascularization, Pathologic; Prostatic Neoplasms; Vascular Endothelial Growth Factor A
Type
journal article