【摘要】 目的探讨过氧化物酶增殖物活化受体γ(PPARγ)在人胰腺癌生长中的调节作用,以及核因子-κB(NF-κB)和活化蛋白(AP-1)在该过程的变化,旨在进一步揭示PPARγ抑制胰腺癌生长的机制。方法培养细胞经PPARγ配体15-脱氧-前列腺素J2(15d-PGJ2)、RXRα配体9-顺式-维甲酸(9-cis-RA)及其联合作用后,用MTT法测定细胞活力,并评价药物的抗增殖效果;用TransAMTM方法检测其对SW1990细胞中核因子-κB(NF-κB)p65活性蛋白表达的影响;用逆转录聚合酶链式反应(RT-PCR)检测其对SW1990细胞活化蛋白-1(AP-1)表达的调节作用。结果15d-PGJ2和9-cis-RA及其联合应用对胰腺癌细胞的增殖均具有抑制作用,且呈剂量依赖性。9-cis-RA对15d-PGJ2抑制胰腺癌细胞增殖具有协同效应。TransAMTM检测显示,15d-PGJ2、9-cis-RA及其联合作用干预组NF-κBp65活性蛋白含量均表现为先降后升的趋势,但都未达到对照组的水平。RT-PCR揭示随着15d-PGJ2、9-cis-RA及其联合作用浓度的提高,c-junmRNA表达水平均呈现先增高后降低的趋势;在15d-PGJ2或9-cis-RA单独干预组中,c-fosmRNA表达水平逐渐减弱;而在两者联合作用组中表现为逐渐增强的趋势。结论PPARγ的活化在体外对胰腺癌的生长呈负调节作用。RXRα的激活可协同增强PPARγ激动剂的抗增殖作用。其机制可能更多还原

【Abstract】 AIM: To examine the effects of PPARγ activation on the growth of human pancreatic carcinoma in vitro and to explore the role of NF-κB and activator protein-1 （AP-1） in this process. METHODS: SW-1990 pancreatic cancer cells were treated with ligand of RXRα, 9-cis-RA, ligand of PPARγ, 15d-PGJ₂, and both. Antiproliferative effect was evaluated by using MTT assay; the expression of NF-κB p65 active protein was assayed by using TransAM^TM technique. Expression of c-jun and c-fos by SW1990 cells, which were treated with 15d-PGJ₂, 9-cis-RA and both at varying concentrations, were detected by RT-PCR. RESULTS: MTT assay demonstrated that 15d-PGJ₂, 9-cis-RA and the combination of both had a potent inhibitory effect on the growth of SW1990 cells in a dose-dependent manner. 9-cis-RA had a synergic action with 15d-PGJ₂ on the growth inhibition of pancreatic carcinoma. TransAM^TM showed a down-regulation trend of P65 active protein in SW1990 cells treated with 15d-PGJ₂, 9-cis-RA and both. RT-PCR demonstrated that the expression of c-jun mRNA in 15d-PGJ₂, 9-cis-RA and the combination of both-treated cells were firstly increased and then decreased, the expression of c-fos was decreased in 15d-PGJ₂ or 9-cis-RA treated SW1990 cells, but increased in cells treated with both 15d-PGJ₂ and 9-cis-RA. CONCLUSION: Activation of PPARγ exerts a negative regulatory effect on the growth of pancreatic carcinoma in vitro. Activation of RXRα has a synergic action with PPARγ agonist. The mechanism is probably associated with down-regulating the expression of NF-κB and AP-1. [更多还原