ABSTRACT
Objective To investigate the effect of membrane-bound prostaglandin E2 synthase 1 (mPGES-1) inhibitor MK886 on cell cycle of the human acute myeloid leukemia HL-60/A cells.Methods Flow cytometry,Western blot and ELISA were used to measure the difference of cell cycle,expression of cyclin D1, mPGES-1 among HL-60/A cells,MNC and HL-60 cells.The effect of MK886 on cell cycle,cyclin D1,mPGES-1,PGE2,P-Akt and c-myc of HL-60/A cells were observed.Results Compared with MNC and HL-60 cells,the expression of cyclin D1 and mPGES-1 were higher in HL-60/A cells,the percentage of G0-G1 phase was decreased [MNC (62.63±6.58) ％,HL-60 (38.86±2.25) ％,HL-60/A (30.53±2.15) ％]and S phase increased[MNC (12.18±4.43) ％,HL-60 (47.70±1.88）％,HL-60/A (57.56±1.54) ％](all P＜ 0.05).After treated with MK886,cell cycle was arrested in G0-G1 phase.The expression of mPGES-1,cyclin D1,P-Akt and c-myc and synthesis of PGE2 were decreased.Conclusion MK886 can arrest HL-60/A cell cycles in G0-G1 phase,which possibly through down-regulation of mPGES-1/PGE2,reduction cyclin D1,P-Akt and c-myc expression.
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Objective To investigate the effects of two inhibitors of arachidonic acid metabolic pathway (5-cyclooxygenase blockade MK886 and COX 2 blockade celecoxib) on growth and VEGF mRNA expression of human pancreatic cancer cell SW1990.MethodsPancreatic cancer cells SW1990 were cultured with different concentrations of MK886,celecoxib,MK886 and celecoxib,then the cell proliferation was detected by using CCK-8,BLT1 mRNA,PGE2 mRNA and VEGF mRNA expressions were determined by RTPCR.ResultsAfter 10 μmol/L MK886 or 20 mmol/L celecoxib treatment for 24 h,the growth of SW1990 was greatly suppressed ( 1.80 ±0.06 vs 1.65 ±0.10,2.04 ±0.03 vs 1.86 ±0.02,P ＜0.01 ),and the growth suppression of SW1990 cells was increased accompanying the raised concentration of MK886 or celecoxib.After both MK886 and celecoxib treatment for 12 h,the growth of SW 1990 cells was much obviously suppressed (1.72 ±0.05 vs 1.52 ±0.05,P ＜0.01 ).After celecoxib treatment for 48 h,the BLT1 mRNA,PGE2 mRNA and VEGFmRNA expressions were not significantly changed,but the expressions of PGE2 mRNA were significantly decreased ( P ＜ 0.05 ).After MK886 or MK886 + celecoxib treatment,the expressions of BLT1 mRNA,VEGF mRNA were significantly decreased ( P ＜ 0.05 ),but the expressions of PGE2 mRNA were not significantly changed when compared to control group.ConclusionsTwo metabolic pathways of arachidonic acid have a close relation with occurrence and proliferation of pancreatic cancer,when both of the pathways were blocked,the proliferation of the pancreatic cancer cell was suppressed obviously.
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Aim To investigate the effect of fenofibrate on focal cerebral ischemia injury in rats and its mechanism.Methods The rat model of global cerebral ischemia/reperfusion injury was established by bilateral common carotid arteries occlusion combined with hemorrhagic hypotension.Fenofibrate (33, 100, 300 mg·kg~(-1)) was intragastriclly administered 30 min before the operation, MK886 (6 mg·kg~(-1)) was given intraperitoneally 30 min before administration of fenofibrate (300 mg·kg~(-1)).Morris water maze was used to evaluate the ability of spatial learning and memory function.HE staining was used to observe pathological morphological changes of hippocampal neurons. NF-κBp65 expression was detected by immunohistochemistry, SOD activities and MDA contents were analyzed by biochemistry, and IL-1β, IL-6, IL-10, TNF-α levels were detected by ELISA.Results Fenofibrate remarkably improved the spatial learning and memory function, obviously prevented the hippocampal neurons from karyopycnosis and losing induced by I/R. Fenofibrate significantly blunted the increase of MDA, NF-κBp65, TNF-α, IL-1β, IL-6, and the decrease of IL-10 and SOD activities of I/R rats.Conclusions Fenofibrate has an obviously neuroprotective effect on global cerebral ischemia/reperfusion damage by activating PPARα.The anti-inflammation and antioxidative stress of fenofibrate may be involved in the protective mechanism.