Celecoxib inhibits proliferation of polycystic kidney cyst lining epithelial cells through blocking mitogen-activated protein kinase signal transduction pathways
- VernacularTitle:塞来昔布通过阻断丝裂原活化蛋白激酶信号途径抑制多囊肾囊肿衬里上皮细胞增殖
- Author:
Tao XU
- Publication Type:Journal Article
- Keywords:
celecoxib;
mitogen-activated protein kinase;
cyst lining epithelial cell;
polycystic kidney,autosomal dominant
- From:
Academic Journal of Second Military Medical University
1985;0(06):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate whether celecoxib(CXB), a specific COX-2 inhibitor,can inhibit the proliferation of cyst lining epithelial cells through blocking mitogen-activated protein kinase(MAPK) signal transduction pathway.Methods: Primarily cultured cells were treated with different concentrations of CXB(0,2.5?10~(-6),5?10~(-6),1?10~(-5),2?10~(-5),3?10~(-5),4?10~(-5),5?10~(-5)mol/L) and the proliferative status was evaluated by BrdU assay.The levels of vascular endothelial growth factor(VEGF) were measured by enzyme-linked immunosorbent assay(ELISA);the production of proliferating cell nuclear antigen(PCNA) and phosphoMAPK were measured by real-time reverse transcription-PCR assay;and the expression of PCNA,MAPK and phospho-MAPK protein was detected by Western blotting.Results: BrdU assay revealed that CXB inhibited cell growth in a concentration-dependent manner;the maximum inhibition rate([63.9?1.2]%) was found when cells were treated with 2?10~(-5) mol/L CXB for 24 h.VEGF secretion by cyst lining epithelial cell was reduced by CXB in a concentration and time-dependent manner.The mRNA and protein levels of PCNA,phospho-MAPK in CXBtreated group were lower than those in control group(with no CXB treatment).Conclusion: CXB can obviously inhibit the proliferation of cyst lining epithelial cell and the secretion of VEGF,which might be through interfering with the phosphorylation of MAPK and partly blocking MAPK signal transduction pathway.