Objective To investigate the different influences of simvastatin on proliferation of rat smooth muscle progenitor cells(SPCs) versus endothelial progenitor cells (EPCs) and identify the compounds that differentially inhibit SPCs and EPCs proliferation for clinical usefulness. Methods Total mononuclear cells (MNCs) were isolated from bone marrow of rats by Fieoll density gradient centrifugation, and then the cells were plated on fibronectin-coated culture dishes. SPCs outgrew from the culture of MNCs in the presence of platelet-derived growth factor-BB and basic fibroblast growth factor, whereas EPCs were obtained in the presence of vascular endothelial growth factor. SPCs were identified as adherent cells positive for α-smooth muscle actin (α-SMA) by indirect immunofluoreseent staining. EPCs were characterized as adherent cells double positive for DiLDL-uptake and lectin binding by direct fluorescent staining. SPCs and EPCs were stimulated by simvastatin (0.01～10.00 μmol/L) or vehicle control for the respective time points (6 h, 12 h, 24 h and 48 h). SPCs and EPCs proliferation were assayed with 3H-TdR incorporation and manual counting respectively. Results Simvastatin obviously inhibited SPCs proliferation. At the concentration of 0. 01 μmol/L for 12 h,simvastatin significantly reduced the number of SPCs by (5.8±3.1)% compared with control group (P<0.05). Simvastatin significantly stimulated EPCs proliferation, which was dose- and time dependent and reached maximum at 1 μmol/L after 24 hours (2.0±0.1 fold increase, P<0.01).Conclusions Simvastatin displays different effects on SPCs (inhibited) and EPCs (promoted)proliferation. Local application of simvastatin may inhibit arterial restenosis and promote reendothelialization of injured vessels.

Autopsy ; Female ; Heart Failure ; etiology ; pathology ; Humans ; Infant ; Myocardial Infarction ; etiology ; pathology ; Vascular Calcification ; complications ; pathology

AIM:To investigate the effect of sinomenine on the viability, migration and invasion of human ovarian cancer SKOV3 cells and its possible mechanism.METHODS:The SKOV3 cells were treated with sinomenine at different concentrations for 12 h,24 h and 48 h.CCK-8 assay was employed to detect the effects of sinomenine on the via-bility of the SKOV3 cells.Flow cytometry was used to analyze the cell cycle distribution.The cell migration and invasion abilities were measured by Transwell assay.Western blot was used to determine the protein levels of cyclin A,cyclin D1, E-cadherin and matrix metalloproteinase-9(MMP-9).RESULTS: Sinomenine remarkably inhibited the viability of SK-OV3 cells and IOSE80 cells in a time-dependent and dose-dependent manner(P<0.05),and the IC50values of 48 h were 2.12 mmol/L and 17.35 mmol/L,respectively.In a dose-dependent manner,sinomenine induced G0/G1and S phase ar-rest in SKOV3 cells(P<0.05),suppressed the migration and invasion abilities of SKOV 3 cells(P<0.05),down-regu-lated the protein levels of cyclin A,cyclin D1 and MMP-9(P<0.05), and up-regulated the protein level of E-cadherin (P<0.05).CONCLUSION:Sinomenine inhibits the viability,migration and invasion of human ovarian cancer SKOV 3 cells most likely via down-regulation of the protein levels of cyclin A,cyclin D1 and MMP-9,and up-regulation of the pro-tein level of E-cadherin.

OBJECTIVETo investigate the effect of sirolimus on differentiation, proliferation, adhesion and migration of endothelial progenitor cells (EPC) in vitro.

METHODS(1) Mononuclear cells (MNC) were isolated from rat bone marrow by Ficoll density gradient centrifugation and cultured on fibronectin-coated culture dishes with or without sirolimus (0.01 - 100 ng/ml) for 12 days. (2) After 8 days cultured, attached cells were treated with sirolimus (0.1 - 200 ng/ml) or vehicle for various time points (12 h, 24 h, 48 h and 96 h). EPC were identified as adherent cells double positive stained for FITC-UEA-I and DiI-acLDL under laser confocal immunofluence microscope. EPC proliferation, migration were assayed with MTT assay and modified Boyden chamber assay respectively.

RESULTSEPC number differentiated from MNC at 12 days was significantly lower in sirolimus treated cells in a dose-dependent manner than that of vehicle-treated cells. Sirolimus also significantly inhibited the proliferative, migratory and adhesive capacity of EPC in a time and dose dependent manner.

CONCLUSIONPresent results suggested that sirolimus could inhibit EPC differentiation from MNC and reduce the proliferation, migration and adhesion capacities of EPC.

Animals ; Bone Marrow Cells ; drug effects ; Cell Differentiation ; drug effects ; Cell Movement ; drug effects ; Cells, Cultured ; Endothelial Cells ; cytology ; drug effects ; Female ; Male ; Rats ; Rats, Wistar ; Sirolimus ; pharmacology ; Stem Cells ; drug effects