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一种新型姜黄素衍生物ZYX01通过AMPK/ULK1/Beclin-1信号通路诱导人非小细胞肺癌细胞A549发生自噬。

One novel curcumin derivative ZYX01 induces autophagy of human non-small lung cancer cells A549 through AMPK/ULK1/Beclin-1 signaling pathway.

作者信息

Zhou Guang-Zhou, Wang Qing-Qing, Wang Peng-Bo, Wang Zhi-Chen, Sun Gang-Chun

机构信息

College of Bioengineering, Henan University of Technology, Zhengzhou 450001, Henan,China.

College of Chemistry and Chemical Engineering, Henan University of Technology, Zhengzhou 450001, Henan, China.

出版信息

Cell Mol Biol (Noisy-le-grand). 2019 Feb 28;65(2):1-6.

PMID:30860465
Abstract

Presently, curcumin derivatives had been paid more attention in view of their high bioavailability or water solubility, which herein possibly replaced the curcumin for their functional applications in future. Here, one novel chemically synthesized curcumin derivative, ZYX01, was used to identify anti-proliferation activity of human non-small lung cancer cells A549 and its anti-proliferative mechanism. Our study showed that ZYX01 could induce autophagic death of A549 cells by morphological observation, MTT assay, acridine orange staining and MDC assay, which possess a dose-and time-dependent manner. ZYX01-treated A549 cells possessed an increase in LC3-II/LC3-I ratio, upregulation of beclin-1 and downregulation of p62 expression. We further confirmed the cellular AMPK/ULK1/Beclin-1 signaling pathway in A549 cells after ZYX01 treatment. The anti-migration effect of ZYX01 in A549 cells was also explored by wound healing assay and transwell experiment. Current results had confirmed that ZYX01 induced A549 cells autophagy through AMPK/ULK1/Beclin-1 pathway and shed light on the future study on the anti-cancer molecular mechanism.

摘要

目前,姜黄素衍生物因其高生物利用度或水溶性而受到更多关注,在未来其功能应用中可能会取代姜黄素。在此,一种新型化学合成的姜黄素衍生物ZYX01被用于鉴定人非小细胞肺癌细胞A549的抗增殖活性及其抗增殖机制。我们的研究表明,通过形态学观察、MTT法、吖啶橙染色和MDC法,ZYX01可诱导A549细胞自噬死亡,且具有剂量和时间依赖性。ZYX01处理的A549细胞中LC3-II/LC3-I比值升高,beclin-1上调,p62表达下调。我们进一步证实了ZYX01处理后A549细胞中的细胞AMPK/ULK1/Beclin-1信号通路。通过伤口愈合试验和Transwell实验也探索了ZYX01对A549细胞的抗迁移作用。目前的结果证实,ZYX01通过AMPK/ULK1/Beclin-1途径诱导A549细胞自噬,并为未来抗癌分子机制的研究提供了线索。

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