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Effects of simvastatin on PDGF-BB and serum-induced proliferation of vascular smooth muscle cells and on the expression of tumor suppressor gene PTEN
Authors:CHENG Gang  XU Geng  SHAN Jiang  HUANG Jin-yu
Institution:Department of Cardiology, the Second Affiliated Hospital, Zhejiang University, Medical School, Hangzhou 310009, China
Abstract:AIM:To observe the effect of simvastatin on the proliferation of vascular smooth muscle cells(VSMCs) induced by serum and growth factor PDGF-BB and the effect of simvastatin on the expression of PTEN,a important regulator of G1/S cell cycle transition. METHODS:The DNA synthesis was determined by 3H]-TdR incorporation, cell cycle was examined with flow cytometry, the protein level of PTEN was measured by Western blot method. RESULTS: (1)Simvastatin inhibited 3H]-TdR incorporation in a dose dependent manner. (2) Flow cytometric DNA analysis revealed that simvastatin induced significantly enhancement of G0/G1 phase and decrease in S phase VSMCs.(3)Simvastatin increased protein level of PTEN and mevalonate, a metabolite of HMG-COA, reversed the effect of simvastatin on PTEN protein expression. CONCLUSION:Simvastatin may inhibit proliferation of VSMCs and retarded cell cycle in G0/G1 phase by increasing PTEN expression through inhibiting synthesis of mevalonate.
Keywords:Simvastatin  Muscle  smooth  vascular  Genes  suppressor  tumor  
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