Atorvastatin Calcium Inhibits PDGF-ββ-Induced Proliferation and Migration of VSMCs Through the G0/G1 Cell Cycle Arrest and Suppression of Activated PDGFRβ-PI3K-Akt Signaling Cascade
| Autor: | Xiaofan Guo, Naijin Zhang, Yingxian Sun, Zhao Li, Siyuan Dong, Shuang Chen, Bo Yu |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Male Cell cycle checkpoint Cyclin E Physiology PDGF-ββ Becaplermin lcsh:Physiology Muscle Smooth Vascular lcsh:Biochemistry Rats Sprague-Dawley Receptor Platelet-Derived Growth Factor beta 03 medical and health sciences Phosphatidylinositol 3-Kinases 0302 clinical medicine Cell Movement Proliferating Cell Nuclear Antigen Vascular smooth muscle cells Atorvastatin Animals lcsh:QD415-436 Cyclin D1 Phosphorylation Protein kinase B Cells Cultured Cell Proliferation Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 biology lcsh:QP1-981 Cell growth Chemistry Phospholipase C gamma Akt Cell migration Proto-Oncogene Proteins c-sis G1 Phase Cell Cycle Checkpoints Cell biology Rats 030104 developmental biology 030220 oncology & carcinogenesis Atorvastatin calcium biology.protein G1 phase Proto-Oncogene Proteins c-akt Platelet-derived growth factor receptor Signal Transduction |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 44, Iss 1, Pp 215-228 (2017) |
| ISSN: | 1421-9778 |
| Popis: | Background/Aims: Abnormal proliferation of vascular smooth muscle cells (VSMCs) is a hallmark of vascular lesions, such as atherosclerosis and restenosis. PDGF-ββ, an isoform of PDGF (platelet-derived growth factor), has been demonstrated to induce proliferation and migration of VSMCs. Atorvastatin calcium, a selective inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, has favorable protective effects on VSMCs. This study examined the effects of atorvastatin calcium on the proliferation and migration of PDGF-ββ-treated VSMCs, as well as its underlying mechanisms. Methods: MTT assays, Edu imaging, cell cycle analysis, wound healing assays, transwell migration assays, and western blot analysis were performed. Results: Atorvastatin calcium significantly inhibited cell proliferation, DNA synthesis and cell migration of PDGF-ββ-treated VSMCs. We demonstrated that atorvastatin calcium induced cell cycle arrest in the G0/G1 phase in response to PDGF-ββ stimulation and decreased the expression of G0/G1-specific regulatory proteins, including proliferating cell nuclear antigen (PCNA), CDK2, cyclin D1, cyclin E and CDK4 in PDGF-ββ-treated VSMCs. Moreover, pretreatment with atorvastatin calcium inhibited the PDGF-ββ-treated phosphorylation of PDGFRβ and Akt, whereas atorvastatin calcium did not affect the phosphorylation of PLC-γ1 or (ERK) 1/2. Conclusion: Our data suggested that atorvastatin calcium inhibited abnormal proliferation and migration of VSMCs through G0/G1 cell cycle arrest and suppression of the PDGFRβ-Akt signaling cascade. |
| Databáze: | OpenAIRE |
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