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].现代生物医学进展英文版,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 |
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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) |
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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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