新型双胍衍生物1-环戊烷基-5-(4-三氟甲基苯基)双胍抑制非小细胞肺癌细胞生长与AMPK激活及m TOR/p70S6K信号通路下调相关

A novel guanidine derivative,1-cyclopentyl-5-(4-trifluoromethylphenyl)guanidine inhibits the growth of non-small cell lung cancer cells associated with activation of AMPK and down-regulation of mTOR/p70S6K signaling pathway

目的:肺癌是发病率和死亡率最高的疾病之一。我们之前的研究发现一种新型双胍衍生物1-环戊烷基-5-(4-三氟甲基苯基)双胍(7d)在非小细胞肺癌(NSCLC)细胞系A549中显示出优异的抗增殖活性。然而,该化合物的抗肿瘤机制仍不清楚。本文旨在探讨7d的抗增殖机制。方法:应用MTT实验、细胞克隆实验和Wb实验分别检测衍生物7d对NSCLC细胞增殖、集落形成和相关蛋白磷酸化水平的影响。结果:衍生物7d处理后,NSCLC细胞增殖和集落形成被明显抑制。机制研究表明7d显著激活AMPK磷酸化,并降低mTOR/p70S6K磷酸化水平。结论:新型双胍衍生物1-环戊烷基-5-(4-三氟甲基苯基)双胍抑制非小细胞肺癌细胞生长的机制可能与激活AMPK并下调mTOR/p70S6K信号通路相关。

Objective Lung cancer remains one of the diseases with the highest morbidity and mortality.Our previous study has found that a novel biguanidine derivative,1-cyclopentyl-5-(4-trifluoromethylphenyl)guanidine(7d),exhibits excellent antiproliferative activity in non-small cell lung cancer(NSCLC)cell line A549.However,the antitumor mechanism of this compound remains unclear.The purpose of our study was to investigate the anti-proliferation mechanism of 7d.Methods We used MTT,cell cloning and WB assays to detect that the effects of 7d on proliferation,colony formation and related protein phosphorylation of NSCLC cells.Results After treated with 7d for 7 days,the proliferation and colony formation of NSCLC cells were significantly inhibited.The study of mechanism showed that 7d significantly activated AMPK phosphorylation and decreased mTOR/p70S6K phosphorylation levels.Conclusion A novel biguanidine derivative,1-cyclopentyl-5-(4-trifluoromethylphenyl)guanidine inhibits the growth of NSCLCs associated with activation of AMPK and down-regulation of mTOR/p70S6K signaling pathway.