文章摘要
杭天星 李瑛 牛梦婕 王明星 邹远康 柴雅琴 李圣青.培美曲塞联合罗格列酮抑制肺癌A549 细胞增殖研究[J].,2017,17(6):1033-1037
培美曲塞联合罗格列酮抑制肺癌A549 细胞增殖研究
Proliferation Inhibition of Pemetrexed combined with Rosiglitazone in A549Lung Cancer Cell Lines
  
DOI:
中文关键词: 培美曲塞  罗格列酮  非小细胞肺癌  细胞增殖
英文关键词: Pemetrexed  Rosiglitazone  Non-small cell lung cancer  Proliferation
基金项目:国家自然科学基金项目(81470249)
作者单位
杭天星 李瑛 牛梦婕 王明星 邹远康 柴雅琴 李圣青 第四军医大学西京医院呼吸内科陕西省第二人民医院第四军医大学唐都医院胸外科第四军医大学学员旅西安航天总医院复旦大学附属华山医院呼吸内科 
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中文摘要:
      目的:研究培美曲塞联合过氧化物酶体增殖物激活受体r(Peroxisome proliferators-activated receptor r,PPAR-r)激动剂罗格列 酮(Rosiglitazone , RSG)对人肺癌A549 细胞株增殖能力的影响。方法:蛋白质印迹法检测肺癌细胞系中PPAR酌的表达水平,筛选 高表达PPAR酌的肺癌细胞株,利用该细胞株并分别给予培美曲塞、培美曲塞联合罗格列酮、培美曲塞联合罗格列酮及PPAR -r拮 抗剂GW9662 处理,之后检测细胞增殖能力及PPAR-r、PTEN、pAKT表达水平的变化。结果:PPAR-r在A549 细胞系中显著高表 达;培美曲塞组、培美曲塞联合罗格列酮组、培美曲塞联合罗格列酮及GW9662 组,肺癌细胞增殖均受到抑制;培美曲塞和罗格列 酮联合应用对肺癌细胞的增殖抑制具有协同效应,与单用培美曲塞组相比有统计学差异,且该效应可被GW9662有效阻断;给予 培美曲塞和罗格列酮联合应用,可明显上调PPAR酌、PTEN 表达,下调pAKT 表达;给予PPAR-r拮抗剂GW9662 后,PPAR-r、 PTEN 的表达显著下调,pAKT表达上调。结论:PPAR-r激动剂RSG对培美曲塞抑制肺癌细胞的增殖具有协同效应,且其分子机制 可能是通过激活PPAR-r/PTEN/pAKT信号通路,从而抑制肺癌A549 细胞增殖。
英文摘要:
      Objective:To investigate antitumor effects of the combination with pemetrexed and peroxisome proliferator-activated receptor-r agonist rosiglitazone on non-small cell lung cancer.Methods:The A549 cells were divided into the control,pemetrexed, RGZ + pemetrexed and RGZ + pemetrexed + GW9662 groups. They were incubated with DMSO, pemetrexed, RGZ + pemetrexed and RGZ + pemetrexed + GW9662 groups for 72 h, respectively. Then, the cell proliferation was measured using CCK8 assay and the expression of PPAR酌and PTEN were detected by Western blot.Results:synergistic effect. Also the anti-proliferation effect was decreased in RGZ + pemetrexed + GW9662 group. The expression of PTEN were increased and P-AKT were decreased in pemetrexed、RGZ + pemetrexed group, on the contrary, the expression of PTEN were decreased and pAKT were increased in RGZ + pemetrexed + GW9662 group.Conclusion:Peroxisome proliferator-activated receptor-r agonist rosiglitazone could enhances the growth inhibition of pemetrexed by activated PPARr/PTEN/pAKTsignaling pathway.
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