通过阻断花生四烯酸代谢途径抑制胰腺癌细胞增殖

Inhibition of arachidonic acid metabolism to decrease pancreatic cancer cell proliferation

目的:探讨通过阻断花生四烯酸(arachidonic acid,AA)代谢途径抑制胰腺癌细胞增殖.方法:将胰腺癌细胞SW1990分为对照组,M K886干预组、塞莱昔布(C e l e c o x i b)干预组,MK886+Celecoxib干预组,用RT-PCR法检测细胞白三烯B4受体1(leukotriene B4receptor 1,BLT1)mRNA,血管内皮生长因子(vascular endothelial growth factor,VEGF)mRNA的表达量变化,用Western blot检测磷酸化-Erk(phosphorylated-extracellular regulated protein,p-Erk)表达量变化.结果:MK886作用下,BLT1 mRNA、VEGF mRNA等表达量均减少(P<0.01),p-Erk表达量明显减少(P<0.05),Celecoxib作用下,VEGF mRNA表达量明显减少(P<0.01),BLT1 mRNA表达与对照组无明显差异,p-Erk表达量与MK886组比较明显增加(P<0.01),MK886+80?mol/L Celecoxib作用下,BLT1 mRNA、VEGF mRNA表达量明显减少(P<0.01),p-Erk表达量与对照组无明显差异.结论:花生四烯酸的两条代谢途径均与胰腺癌的发生及增殖均有密切关系,而抑制5-脂氧合酶(5-lipoxygenase)途径较环氧化酶2(cyclooxygenase 2)途径相比,抑制肿瘤细胞增殖作用更强.

AIM： To investigate the effect of inhibition of arachidonic acid metabolism on proliferation of pancreatic cancer cells. METHODS： Cultured pancreatic cancer SW1990 cells were treated with different concentrations of MK886, celecoxib, or MK886 ＋ celecoxib. After treatment, the expression of leukotriene B4 receptor 1 （BLT1） and vascular endothelial growth factor （VEGF） mRNAs was detected by semi-quantitative RT-PCR and the expression of phosphorylated extracellular regulated protein （p-Erk） was measured by Western blot. RESULTS： Treatment with MK886 significantly decreased the expression of BLT1 and VEGF mRNAs （P 〈 0.01 for both） and p-Erk （P 〈 0.05）.Treatment with celecoxib did not alter the expres- sion of BLT1 mRNA and decreased the expres- sion of VEGF mRNA compared with untreated cells （P 〈 0.01）, but increased the expression of p-Erk compared with the MK886 group （P 〈 0.01）. Treatment with MK886 and celecoxib significant- ly decreased the expression of BLT1 and VEGF mRNAs （P 〈 0.01 for both）, but did not alter the expression of p-Erk. CONCLUSION： Both two pathways of ara- chidonic acid metabolism are associated with pancreatic cancer cell proliferation, with the pathway involving 5-1ipoxygenase being more important.