研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

橙黄桦孢菌通过抑制Twist和HIF-1α在Twist过表达的头颈鳞状细胞癌细胞中的表达,抑制上皮间质转化/转移和Warburg效应。

Antrodia salmonea suppresses epithelial-mesenchymal transition/metastasis and Warburg effects by inhibiting Twist and HIF-1α expression in Twist-overexpressing head and neck squamous cell carcinoma cells.

发表日期:2023 Aug 10
作者: Jhih-Hsuan Hseu, Yi-An Lin, Sudhir Pandey, Chithravel Vadivalagan, Asif Ali, Siang-Jyun Chen, Tzong-Der Way, Hsin-Ling Yang, You-Cheng Hseu
来源: ANTIOXIDANTS & REDOX SIGNALING

摘要:

红背木姜(AS),与白桦姜属相连,是一种药用真菌,具有抗炎、抗氧化和抑制肿瘤的特性。本研究调查了AS暴露对扭曲过度表达的头颈鳞状细胞癌(HNSCC,OECM-1和FaDu-Twist)细胞的代谢重编程和抗转移/上皮间质转变(EMT)效应。使用MTT分析、Western blot、迁移/侵袭分析、免疫荧光、葡萄糖摄取分析、乳酸分析、氧气消耗速率(OCR)/细胞外酸化速率(ECAR)分析、液相色谱-电喷雾离子化串联质谱(LC-ESI-MS)和qRT-PCR实验技术评估了AS治疗HNSCC细胞的治疗潜力。本研究显示,AS在扭曲过度表达的HNSCC细胞中表现出抗EMT和抗转移效应以及代谢重编程。AS暴露抑制了扭曲和缺氧诱导因子-1α(HIF-1α)在OECM-1和FaDu-Twist细胞中的蛋白质和/或mRNA表达。AS显著抑制了EMT,通过增强E-cadherin的表达,同时抑制N-cadherin的表达。此外,AS还通过减少OECM-1细胞中HIF-1α调节的糖酵解基因,降低了葡萄糖摄取和乳酸积累。AS减少了OECM-1细胞中的ECAR,并增加了氧气消耗速率、基础呼吸、ATP产生、最大呼吸和备用呼吸容量,在缺氧(CoCl2)和氧气(CoCl2)下。AS治疗在OECM-1细胞中降低了糖酵解中间产物的水平,同时增加了TCA循环代谢物的水平。我们得出结论,AS治疗通过抑制Twist和HIF-1α在扭曲过度表达的HNSCC细胞中抑制了EMT/转移和Warburg效应。版权所有 © 2023。由Elsevier B.V.出版。
Antrodia salmonea (AS), linked to the genus Taiwanofungus, is a medicinal fungus, and exhibits anti-inflammatory, anti-oxidant, and tumor inhibiting properties.In this study, we investigated the metabolic reprogramming and anti-metastasis/epithelial-mesenchymal transition (EMT) effects of AS exposure in Twist-overexpressing head and neck squamous cell carcinoma (HNSCC, OECM-1 and FaDu-Twist) cells.MTT assay, Western blot, migration/invasion assay, immunofluorescence, glucose uptake assay, lactate assay, oxygen consumption rate (OCR)/Extracellular acidification rate (ECAR) assay, Liquid Chromatography-Electrospray Ionization Tandem Mass Spectrometry (LC-ESI-MS), and qRT-PCR experimental techniques were used to evaluate the therapeutic potential of AS treatment in HNSCC cells.This study showed that AS exhibits anti-EMT and anti-metastatic effects as well as metabolic reprogramming in Twist-overexpressing HNSCC cells. AS exposure inhibited Twist and hypoxia-inducible factor-1α (HIF-1α) protein and/or mRNA expression in Twist-overexpressing OECM-1 and FaDu-Twist cells. AS markedly suppressed EMT by enhancing the expression of E-cadherin; while the N-cadherin was suppressed. Furthermore, glucose uptake and lactate accumulation, together with HIF-1α-regulated glycolysis genes were diminished by AS in OECM-1 cells. AS decreased the ECAR, and enhanced the OCR together with basal respiration, ATP production, maximal respiration, and spare respiratory capacity under normoxia and hypoxia (CoCl2) in OECM-1 cells. There was a marked reduction in the level of glycolytic intermediate's; while TCA cycle metabolites were increased by AS treatment in OECM-1 cells.We concluded that AS treatment suppresses EMT/metastasis and Warburg effects through Twist and HIF-1α inhibition in Twist-overexpressing HNSCC cells.Copyright © 2023. Published by Elsevier B.V.