摘要
目的探索一种合成的萘醌衍生物对血小板衍生生长因子BB(PDGF-BB)刺激的大鼠主动脉血管平滑肌细胞株A10细胞增殖的影响,并初步阐明其作用机制。方法通过细胞增殖实验、[~3H]胸腺嘧啶核苷掺入实验、细胞周期进程分析、免疫印迹分析等实验手段,研究此合成萘醌衍生物对PDGF-BB诱导的A10细胞周期进展和细胞周期主要信号转导途径的影响。结果合成萘醌衍生物浓度依赖性地降低了S期细胞比例,升高G_0/G_1期细胞比例,减少了DNA合成。合成萘醌衍生物预处理24 h,抑制了PDGF-BB诱发的A10细胞增殖,最大抑制率为44.4%。1μmol·L^(-1)的合成萘醌衍生物明显降低了由PDGF-BB诱导的ERK1/2、Akt、磷脂酶Cγ1、PDGFβ受体的磷酸化水平(P<0.01)。结论此合成的萘醌衍生物通过阻止A10细胞由G_0/G_1期进入S期,显示出抑制PDGF-BB诱导的血管平滑肌细胞增殖的活性,其作用机制可能与下调ERK1/2、Akt、磷脂酶Cγ1、PDGFβ受体的磷酸化水平有关。
Aim To explore the effect of a synthetic naphthoquinone derivative on the proliferation of rat aortic vascular smooth muscle cells(RAVSMCs)stimulated by platelet-derived growth factor BB(PDGF-BB)and to clarify its mechanism underlying the anti-proliferative effect.Methods The influence of the synthetic naphthoquinone derivative on cell cycle progression and main signal transduction pathway of cell cycle induced by PDGF-BB were investigated by cell proliferation assay,[3H]thymidine incorporation test,cell cycle process analysis and immunoblotting assay.Results S phase cell percentage in the cell cycle was reduced,while G 0/G 1 phase cell percentage was increased by the synthetic naphthoquinone in a dose-dependent(0.1,0.5,1μmol·L^-1)manner.Moreover,DNA synthesis also decreased.The inhibitory rate of PDGF-BB-induced RAVSMCs proliferation achieved the maximum of 44.4%after 24 h pre-treatment by the synthetic naphthoquinone derivative at the concentration of 1μmol·L^-1.The phosphorylation of extracellular regulated kinase 1/2(ERK1/2),Akt,phospholipase C(PLC)γ1 and PDGF receptorβ(PDGFRβ)induced by PDGF-BB was significantly decreased(P<0.01)by addtion of 1μmol·L^-1 synthetic naphthoquinone derivative.Conclusions The synthetic naphthoquinone derivative exhibits anti-proliferation activity against RAVSMCs induced by PDGF-BB via blocking the transformation of G 0/G 1 phase cell into S-phase cell in the cell cycle.The mechanisms might be related to its down-regulatory effect on phosporalation level of ERK1/2,Akt,PLCγ1 and PDGFRβ.
作者
张伟云
王晓禹
王丽荣
许长江
温忠秀
ZHANG Wei-yun;WANG Xiao-yu;WANG Li-rong;XU Chang-jiang;WEN Zhong-xiu(Dept of Pharmacy,Xiamen Medical College,Key Lab of TraditionalChinese Medicine Finish Processing and Health Product Development of Fujian Province,Xiamen361023,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2019年第3期359-364,共6页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 81773601)
福建省教育厅中青年教师教育科研项目(A类)(No JT180664)
关键词
合成的萘醌衍生物
血小板源生长因子
血管平滑肌细胞
增殖
作用机制
血管疾病
synthetic naphthoquinone derivative
platelet-derived growth factor
rat aortic vascular smooth muscle cells
proliferation
action mechanism
vascular disorder
