[PD 0332991对血管内皮细胞增殖和凋亡的作用]
[Role of PD 0332991 on the Proliferation and Apoptosis of Vascular Endothelial Cells].
作者信息
Zhao Chenlong, Liu Minghui, Li Yongwen, Zhang Hongbing, Li Ying, Gong Hao, Yuan Yin, Li Weiting, Liu Hongyu, Chen Jun
机构信息
Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China.
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
出版信息
Zhongguo Fei Ai Za Zhi. 2018 May 20;21(5):375-382. doi: 10.3779/j.issn.1009-3419.2018.05.04.
BACKGROUND
Angiogenesis is an important process in the development of tumor. PD 0332991, a cell cycle inhibitor, can specifically inhibit CD4/6 phosphorylation and cell cycle progression. In xeongraft mice models, PD 0332991 treated mice had significantly decreased angiogenesis and vascular density compared with the control group, but the mechanism remains unknown. The purpose of this study is to investigate the role and molecular mechanism of PD 0332991 on vascular endothelial cells.
METHODS
EA.hy926 cells, a kind of vascular endothelial cell, were used as the research model. The effects of PD 0332991 on the activity and proliferation of EA.hy926 cells were detected by the MTT, EdU assays. Wound-healing assays and transwell assays were used to determine the effects of PD 0332991 on the mobility of EA.hy926. The influence of PD 0332991 on cell cycle and apoptosis of endothelial cells was tested by flow cytometry, and the Western blot was applied to observe the expression of cell cycle related proteins in EA.hy926 cells treated by PD 0332991.
RESULTS
PD 0332991 significantly inhibited the proliferation and mobility of EA.hy926 cells, caused cell cycle arrest and apoptosis. At the same time, PD 0332991 inhibited the expression of CDK4/6 and phosphorylation of Rb, and thus inhibited the cell cycle progression of EA.hy926 cells.
CONCLUSIONS
PD 0332991 can inhibit the proliferation and activity of endothelial cells and induces apoptosis.
背景
血管生成是肿瘤发展过程中的一个重要过程。PD 0332991是一种细胞周期抑制剂，可特异性抑制CD4/6磷酸化和细胞周期进程。在异种移植小鼠模型中，与对照组相比，接受PD 0332991治疗的小鼠血管生成和血管密度显著降低，但其机制尚不清楚。本研究旨在探讨PD 0332991对血管内皮细胞的作用及分子机制。
方法
以一种血管内皮细胞EA.hy926细胞作为研究模型。采用MTT法、EdU法检测PD 0332991对EA.hy926细胞活性和增殖的影响。采用划痕实验和Transwell实验测定PD 0332991对EA.hy926细胞迁移能力的影响。通过流式细胞术检测PD 0332991对内皮细胞周期和凋亡的影响，并应用蛋白质免疫印迹法观察PD 0332991处理的EA.hy926细胞中细胞周期相关蛋白的表达。
结果
PD 0332991显著抑制EA.hy926细胞的增殖和迁移能力，导致细胞周期停滞和凋亡。同时，PD 0332991抑制CDK4/6的表达和Rb的磷酸化，从而抑制EA.hy926细胞的细胞周期进程。
结论
PD 0332991可抑制内皮细胞的增殖和活性并诱导其凋亡。
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