Abstract:Objective To explore the effects of NF-κB on proliferation of rat pulmonary artery smooth muscle cells (PASMC) inhibited by simvastatin. Methods PASMC isolated from rats and cultured in vitro were randomly divided into four groups (n=6 each): control, platelet-derived growth factor (PDGF) treatment, PDGF+simvastatin treatment, and PDGF+simvastatin+parthenolide (NF-κB inhibitor) treatment. MTT colorimetric assay and flow cytometry were performed to detect cell proliferation and cell cycle distribution. Immunohistochemistry was performed to detect the expression of NF-κB protein. Real-Time PCR was performed to detect NF-κB mRNA expression. Results Compared with the control group, MTT values of PASMC at all time points, cell proportion at the S phase and G2+M phase, NF-κB protein and mRNA expression increased significantly in the PDGF group (P<0.05). With the intervention of simvastatin, the levels of above indexes decreased compared with the PDGF group (P<0.05). With the intervention of simvastatin and parthenolide, the levels of above indexes decreased more obviously, but were not significantly different from those in the simvastatin intervention group. Conclusions Simvastatin can inhibit proliferation of PASMC and cell cycle process. NF-κB may play an important role in the inhibitory effect of simvastatin on the proliferation of PASMC.
LIU Zhong-Qiang,WANG Xiao-Qin,LIU Han-Min. Effect of NF-κB on proliferation of rat pulmonary artery smooth muscle cells inhibited by simvastatin[J]. CJCP, 2015, 17(2): 185-189.
Gao C, Xu W, Xiao W, et al. Simvastatin decreases stent-induced in-stent restenosis rate via downregulating the expression of PCNA and upregulating that of p27kip1[J]. J Interv Cardiol, 2013, 26(4): 384-391.
[5]
Zhang Z, Zhang M, Li Y, et al. Simvastatin inhibits the additive activation of ERK1/2 and proliferation of rat vascular smooth muscle cells induced by combined mechanical stress and oxLDL through LOX-1 pathway[J]. Cell Signal, 2013, 25(1): 332-340.
[6]
Shen RR, Zhou AY, Kim E, et al. TRAF2 is an NF-κB-activating oncogene in epithelial cancers[J]. Oncogene, 2015, 34(2): 209-216.
[7]
Jeong IK, Oh da H, Park SJ, et al. Inhibition of NF-κB prevents high glucose-induced proliferation and plasminogen activator inhibitor-1 expression in vascular smooth muscle cells[J]. Exp Mol Med, 2011, 43(12): 684-692.
Zeng WJ, Xiong CM, Zhao L, et al. Atorvastatin in pulmonary arterial hypertension(APATH) study[J]. Eur Respir J, 2012, 40(1): 67-74.
[12]
Zhao G, Yu YM, Kaneki M, et al. Simvastatin protects hepatocytes from apoptosis by suppressing the TNF-α/caspase-3 signaling pathway in mice with burn injury[J]. Ann Surg, 2013, 257(6): 1129-1136.
[13]
Kou R, Shiroto T, Sartoretto JL, et al. Suppression of Gαs synthesis by simvastatin treatment of vascular endothelial cells[J]. J Biol Chem, 2012, 287(4): 2643-2651.
[14]
DiDonato JA, Mercurio F, Karin M. NF-κB and the link between inflammation and cancer[J]. Immunol Rev, 2012, 246(1): 379-400.
[15]
Yang C, Ling H, Zhang M, et al. Oxidative stress mediates chemical hypoxia-induced injury and inflammation by activating NF-κb-COX-2 pathway in HaCaT cells[J]. Mol Cells, 2011, 31(6): 531-538.
[16]
Gong J, Xie J, Bedolla R, et al. Combined targeting of STAT3/NF-κB/COX-2/EP4 for effective management of pancreatic cancer[J]. Clin Cancer Res, 2014, 20(5): 1259-1273.
[17]
Andreasen AS, Kelly M, Berg RMG, et al. Type 2 diabetes is associated with altered NF-κB DNA binding activity, JNK phosphorylation, and AMPK phosphorylation in skeletal muscle after LPS[J]. PLoS One, 2011, 6(9): e23999.
[18]
Baumann B, Salem HH, Boehm BO. Anti-inflammatory therapy in type 1 diabetes[J]. Curr Diab Rep, 2012, 12(5): 499-509.
[19]
Fang D, Yang S, Quan W, et al. Atorvastatin suppresses Toll-like receptor 4 expression and NF-κB activation in rabbit atherosclerotic plaques[J]. Eur Rev Med Pharmacol Sci, 2014, 18(2): 242-246.