Thymoquinone inhibits the metastasis of renal cell cancer cells by inducing autophagy via AMPK/mTOR signaling pathway

百里香醌通过AMPK/mTOR信号通路诱导自噬抑制肾细胞癌细胞转移

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作者:Yujiao Zhang, Yizeng Fan, Shangke Huang, Guanying Wang, Rui Han, Fuxi Lei, Anqi Luo, Xin Jing, Lin Zhao, Shanzhi Gu, Xinhan Zhao

Abstract

Thymoquinone (TQ, 2-methyl-5-isopropyl-1,4-benzoquinone), a bioactive constituent extracted from the seeds of Nigella sativa, has been proved to exert anti-tumor efficiency in various cancers. Autophagy is a self-digestion phenomenon, and its role in tumor formation and progression remains controversial. In the present study, we investigated the effects of TQ on renal cell cancer (RCC) cell lines (786-O and ACHN) using wound healing assay, transwell assay and western blot analysis. We found that TQ effectively inhibited the metastatic capacity of RCC cells in vitro, which was also verified in a xenograft model. Meanwhile, we observed LC3 puncta and detected the expression of LC3 in TQ-treated RCC cells, and then found that autophagy was induced by TQ in 786-O and ACHN cell lines. In addition, TQ inhibited the migration and invasion as well as the EMT in RCC cells in an autophagy-dependent manner. To further explore the underlying mechanism, we detected the AMPK/mTOR signaling pathway. The results indicated that TQ inhibited the metastasis of RCC cells by inducing autophagy via AMPK/mTOR signaling pathway. In conclusion, our findings provide a novel therapeutic strategy that aims at TQ-induced autophagy in RCC treatment.

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