title: Inhibitory effects of roscovitine on proliferation and migration of vascular smooth muscle cells in vitro.
abstract: Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are the major cause of in-stent restenosis (ISR). Intervention proliferation and migration of VSMCs is an important strategy for antirestenotic therapy. Roscovitine, a second-generation cyclin-dependent kinase inhibitor, can inhibit cell cycle of multiple cell types. We studied the effects of roscovitine on cell cycle distribution, proliferation and migration of VSMCs in vitro by flow cytometry, BrdU incorporation and wound healing assay, respectively. Our results showed that roscovitine increased the proportion of G0/G1 phase cells after 12 h (69.57±3.65 vs. 92.50±1.68, P=0.000), 24 h (80.87±2.24 vs. 90.25±0.79, P=0.000) and 48 h (88.08±3.86 vs. 88.87±2.43, P=0.427) as compared with control group. Roscovitine inhibited proliferation and migration of VSMCs in a concentration-dependent way. With the increase of concentration, roscovitine showed increased capacity for growth and migration inhibition. Roscovitine (30 μmol/L) led to an almost complete VSMCs growth and migration arrest. Combined with its low toxicity and selective inhibition to ISR-VSMCs, roscovitine may be a potential drug in the treatment of vascular stenosis diseases and particularly useful in the prevention and treatment of ISR.
authors.affiliation: Department of Cardiovascular Medicine, Huazhong University of Science and Technology, Wuhan, 430030, China.|Department of Cardiovascular Medicine, The Central Hospital of Wuhan, Wuhan, 430014, China.
authors.forename: Shuang-Shuang
authors.initials: SS
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Medicine, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Chong-Qiang
authors.initials: CQ
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Min-Jie
authors.initials: MJ
authors.lastname: Xie
authors.affiliation: Department of Cardiovascular Medicine, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Li
authors.affiliation: Department of Cardiovascular Medicine, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Xiang-Li
authors.initials: XL
authors.lastname: Yang
authors.affiliation: Department of Cardiovascular Medicine, Huazhong University of Science and Technology, Wuhan, 430030, China. lujiagao@tjh.tjmu.edu.cn.
authors.forename: Jia-Gao
authors.initials: JG
authors.lastname: Lv
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D006083:Graft Occlusion, Vascular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology*; D051381:Rats; D000077546:Roscovitine
chemical_list: D047428:Protein Kinase Inhibitors; D011687:Purines; D000077546:Roscovitine