Piperine Inhibits Platelet-Derived Growth Factor-BB-Induced Proliferation and Migration in Vascular Smooth Muscle Cells
Piperine Inhibits Platelet-Derived Growth Factor-BB-Induced Proliferation and Migration in Vascular Smooth Muscle Cells
复制标题
DOI：
10.1089/jmf.2014.3229
复制
发表时间：
2015-02-01
影响因子：
2.4
通讯作者：
Hong, Heeok
中科院分区：
文献类型：
--
作者：
Lee, Kang Pa;Lee, Kwan;Hong, Heeok
血管平滑肌细胞（VSMCs）在血管内的增殖和迁移在动脉粥样硬化和再狭窄等血管疾病的发病机制中起重要作用。胡椒碱是黑胡椒的主要成分，具有抗氧化、抗癌和抗炎作用。然而，胡椒碱的抗动脉粥样硬化作用尚未被研究。本研究探讨胡椒碱对血小板衍生生长因子(PDGF)- bb诱导的VSMCs增殖和迁移的影响。采用MTT法、细胞计数法、实时聚合酶链反应法和western blots法检测胡椒碱的抗增殖作用。我们的研究结果表明，胡椒碱通过增加p27（kip1）的表达，调节细胞周期酶（cyclin D， cyclin E和PCNA）的mRNA表达，并以非细胞毒性浓度依赖性的方式降低细胞外信号调节激酶（ERK）1/2的磷酸化，显著减弱VSMCs的增殖（30-100 μ M）。此外，我们通过Boyden实验、H(2)DCFDA染色和western blots检测了胡椒碱对pdgf - bb刺激的VSMCs迁移的影响。我们的研究结果表明，100 μ M胡椒碱降低了细胞迁移、活性氧（ROS）的产生和p38丝裂原活化蛋白激酶（MAPK）的磷酸化。综上所述，我们的研究结果表明，胡椒碱通过诱导细胞周期阻滞和抑制MAPK磷酸化和ROS抑制pdgf - bb诱导的VSMCs增殖和迁移。这些发现提示胡椒碱可能对血管相关疾病和疾病的治疗有益。
The proliferation and migration of vascular smooth muscle cells (VSMCs) in blood vessels are important in the pathogenesis of vascular disorders such as atherosclerosis and restenosis. Piperine, a major component of black pepper, has antioxidant, anticancer, and anti-inflammatory activity. However, the antiatherosclerotic effects of piperine have not been investigated. In this study, the effects of piperine on platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of VSMCs were investigated. The antiproliferative effects of piperine were determined using MTT assays, cell counting, real-time polymerase chain reaction, and western blots. Our results showed that piperine significantly attenuated the proliferation of VSMCs by increasing the expression of p27(kip1), regulating the mRNA expression of cell cycle enzymes (cyclin D, cyclin E, and PCNA), and decreasing the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 in a noncytotoxic concentration-dependent manner (30-100 mu M). Moreover, we examined the effects of piperine on the migration of PDGF-BB-stimulated VSMCs, as determined by the Boyden chamber assay, H(2)DCFDA staining, and western blots. Our results showed that 100 mu M piperine decreased cell migration, the production of reactive oxygen species (ROS), and phosphorylation of the p38 mitogen-activated protein kinase (MAPK). Taken together, our results suggest that piperine inhibits PDGF-BB-induced proliferation and the migration of VSMCs by inducing cell cycle arrest and suppressing MAPK phosphorylation and ROS. These findings suggest that piperine may be beneficial for the treatment of vascular-related disorders and diseases.