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α-硫辛酸通过 mTOR 介导的自噬抑制抑制肺癌生长。

Alpha-lipoic acid inhibits lung cancer growth via mTOR-mediated autophagy inhibition.

机构信息

Department of Anesthesiology, First Affiliated Hospital with Nanjing Medical University, China.

Department of Geriatrics, Jiangsu Provincial Key Laboratory of Geriatrics, First Affiliated Hospital with Nanjing Medical University, China.

出版信息

FEBS Open Bio. 2020 Apr;10(4):607-618. doi: 10.1002/2211-5463.12820. Epub 2020 Mar 18.

Abstract

Lung cancer is the leading cause of cancer-related death, and there remains a need for novel therapies for this malignancy. Here, we examined the effects of alpha-lipoic acid (LA), a drug used for treating human diabetic complications, on lung cancer growth. We report that LA limited lung cancer growth in xenograft mice and reduced lung cancer A549 cell viability. We observed autophagy activation in human lung cancers, and report that LA inactivated autophagy in A549 cells. In addition, LA activated mammalian target of rapamycin (mTOR)/p70S6K signaling. Inhibition of mTOR with rapamycin reversed LA-induced inactivation of autophagy and abolished LA-induced suppression of A549 cell viability. Altogether, the data suggest that LA exerts an anti-lung cancer effect through mTOR-mediated inhibition of autophagy, and thus LA may have therapeutic potential for lung cancer management.

摘要

肺癌是癌症相关死亡的主要原因,因此仍然需要针对这种恶性肿瘤的新型治疗方法。在这里,我们研究了α-硫辛酸(LA)的作用,α-硫辛酸是一种用于治疗人类糖尿病并发症的药物,对肺癌生长的影响。我们报告说,LA 限制了异种移植小鼠肺癌的生长并降低了肺癌 A549 细胞的活力。我们观察到人类肺癌中自噬的激活,并报告说 LA 使 A549 细胞中的自噬失活。此外,LA 激活了雷帕霉素靶蛋白(mTOR)/p70S6K 信号通路。用雷帕霉素抑制 mTOR 逆转了 LA 诱导的自噬失活,并消除了 LA 诱导的 A549 细胞活力抑制。总之,这些数据表明,LA 通过 mTOR 介导的自噬抑制发挥抗肺癌作用,因此 LA 可能具有治疗肺癌的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ddb/7137803/2e135cea2305/FEB4-10-607-g001.jpg

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