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白藜芦醇通过抑制PI3K/AKT/mTOR信号通路促进自噬,从而抑制黑色素瘤的生长。

Resveratrol suppresses melanoma growth by promoting autophagy through inhibiting the PI3K/AKT/mTOR signaling pathway.

作者信息

Gong Changhua, Xia Honglei

机构信息

Department of Pharmacy, People's Hospital of Zhenhai, Ningbo, Zhejiang 315202, P.R. China.

出版信息

Exp Ther Med. 2020 Mar;19(3):1878-1886. doi: 10.3892/etm.2019.8359. Epub 2019 Dec 20.

DOI:10.3892/etm.2019.8359
PMID:32104244
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7027143/
Abstract

Resveratrol (RV) is a natural polyphenolic phytoalexin derived from peanuts, red grape skins and red wine, and has been demonstrated to alleviate multiple types of malignancies. However, how RV achieves this in melanoma is unknown. The aim of present study was to investigate the role of RV in melanoma, using Cell Counting Kit-8, flow cytometry and western blot analysis. RV inhibited melanoma cell viability, migration and invasion counteracting melanoma progression. In addition, proteins associated with autophagy, including Beclin 1 and microtubule-associated protein 1A/1B-light chain 3 (LC3)-II/I, were upregulated, whereas p62 expression was downregulated in RV-treated cells. The number of LC3 puncta, which can be applied to represent autophagosome formation, increased following RV treatment, suggesting that RV may trigger autophagy in melanoma cells. Treatment with the autophagy inhibitor, 3-methyladenine, reversed the RV-dependent inhibition of viability, migration and invasion of melanoma cells. RV treatment also reduced the ratios of phosphorylated (p)-AKT/AKT and p-mTOR/mTOR in melanoma cells. In conclusion, these findings suggested that RV may inhibit the viability and migration of melanoma cells through inhibiting the AKT/mTOR pathway, thus triggering autophagy. This indicated that RV may serve as an innovative therapeutic for melanoma treatment.

摘要

白藜芦醇(RV)是一种天然的多酚类植物抗毒素,来源于花生、红葡萄皮和红酒,已被证明可缓解多种类型的恶性肿瘤。然而,RV在黑色素瘤中如何实现这一点尚不清楚。本研究的目的是使用细胞计数试剂盒-8、流式细胞术和蛋白质印迹分析来研究RV在黑色素瘤中的作用。RV抑制黑色素瘤细胞的活力、迁移和侵袭,对抗黑色素瘤的进展。此外,与自噬相关的蛋白质,包括Beclin 1和微管相关蛋白1A/1B轻链3(LC3)-II/I,在RV处理的细胞中上调,而p62表达下调。可用于代表自噬体形成的LC3斑点数量在RV处理后增加,表明RV可能触发黑色素瘤细胞中的自噬。用自噬抑制剂3-甲基腺嘌呤处理可逆转RV对黑色素瘤细胞活力、迁移和侵袭的依赖性抑制。RV处理还降低了黑色素瘤细胞中磷酸化(p)-AKT/AKT和p-mTOR/mTOR的比例。总之,这些发现表明RV可能通过抑制AKT/mTOR途径来抑制黑色素瘤细胞的活力和迁移,从而触发自噬。这表明RV可能作为一种创新的黑色素瘤治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0db0/7027143/77054a4936dd/etm-19-03-1878-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0db0/7027143/cd7de3a98d34/etm-19-03-1878-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0db0/7027143/9061d57b0b73/etm-19-03-1878-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0db0/7027143/2c6b9deea610/etm-19-03-1878-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0db0/7027143/5b2b0cf0c64d/etm-19-03-1878-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0db0/7027143/ee3bf92b4eb9/etm-19-03-1878-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0db0/7027143/77054a4936dd/etm-19-03-1878-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0db0/7027143/cd7de3a98d34/etm-19-03-1878-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0db0/7027143/9061d57b0b73/etm-19-03-1878-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0db0/7027143/2c6b9deea610/etm-19-03-1878-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0db0/7027143/5b2b0cf0c64d/etm-19-03-1878-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0db0/7027143/ee3bf92b4eb9/etm-19-03-1878-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0db0/7027143/77054a4936dd/etm-19-03-1878-g05.jpg

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