Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
Prostate. 2013 Jan;73(1):89-100. doi: 10.1002/pros.22544. Epub 2012 Jun 1.
Prostate cancer is the most commonly diagnosed malignancy in men and shows a predilection for metastasis to the bone. Bradykinin (BK) is an inflammatory mediator, and shows elevated levels in regions of severe injury and inflammatory diseases. The aim of this study was to investigate whether Bradykinin is associated with migration of prostate cancer cells.
Cancer cells migration activity was examined using the Transwell assay. The c-Src and PKCδ phosphorylation was examined by using Western blot method. The qPCR was used to examine the mRNA expression of metalloproteinase. A transient transfection protocol was used to examine NF-κB activity.
We found that bradykinin increased the chemomigration and the expression of MMP-9 of human prostate cancer cells. Bradykinin-mediated chemomigration and metalloproteinase expression was attenuated by PKCδ inhibitor (rottlerin), PKCδ siRNA, c-Src inhibitor (PP2) and c-Src mutant. Activations of PKCδ, c-Src and NF-κB pathways after bradykinin treatment was demonstrated, and bradykinin-induced expression of metalloproteinase and chemomigration activity was inhibited by the specific inhibitor and mutant of PKCδ, c-Src, and NF-κB cascades.
This study showed for the first time that the bradykinin mediates migration of human prostate cancer cells. One of the mechanisms underlying bradykinin directed migration was transcriptional up-regulation of MMP-9 and activation of B2 receptor, PKCδ, c-Src, and NF-κB pathways.
前列腺癌是男性最常见的恶性肿瘤，易转移至骨骼。缓激肽（BK）是一种炎症介质，在严重损伤和炎症疾病区域的水平升高。本研究旨在探讨缓激肽是否与前列腺癌细胞的迁移有关。
使用 Transwell 检测法检测癌细胞迁移活性。使用 Western blot 法检测 c-Src 和 PKCδ 的磷酸化。使用 qPCR 检测金属蛋白酶的 mRNA 表达。使用瞬时转染方案检测 NF-κB 活性。
我们发现缓激肽增加了人前列腺癌细胞的趋化迁移和 MMP-9 的表达。PKCδ 抑制剂（rottlerin）、PKCδ siRNA、c-Src 抑制剂（PP2）和 c-Src 突变体可减弱缓激肽介导的趋化迁移和金属蛋白酶表达。缓激肽处理后，PKCδ、c-Src 和 NF-κB 途径被激活，PKCδ、c-Src 和 NF-κB 途径的特异性抑制剂和突变体抑制了缓激肽诱导的金属蛋白酶表达和趋化迁移活性。
本研究首次表明缓激肽介导了人前列腺癌细胞的迁移。缓激肽定向迁移的机制之一是 MMP-9 的转录上调和 B2 受体、PKCδ、c-Src 和 NF-κB 途径的激活。
