研究动态
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二甲双胍是通过调节葡萄糖代谢来治疗 COVID-19/LUAD 的潜在疗法。

Metformin is a potential therapeutic for COVID-19/LUAD by regulating glucose metabolism.

发表日期:2024 May 30
作者: Yongwang Hou, Zhicong Yang, Baoli Xiang, Jiangmin Liu, Lina Geng, Dandan Xu, Minghua Zhan, Yuhuan Xu, Bin Zhang
来源: CLINICAL PHARMACOLOGY & THERAPEUTICS

摘要:

肺腺癌 (LUAD) 是肺癌最常见、最具侵袭性的亚型,2019 年冠状病毒病 (COVID-19) 已成为全球严重的公共卫生威胁。患有 LUAD 和 COVID-19 的患者预后较差。因此,寻找可用于治疗 COVID-19/LUAD 患者的药物至关重要。利用生物信息学分析确定了 20 个可能用于治疗 COVID-19/LUAD 的二甲双胍靶基因。 PTEN和mTOR可能作为二甲双胍的枢纽靶基因。生物信息学研究结果表明,二甲双胍可能通过能量代谢、氧化还原酶NADH活性、FoxO信号通路、AMPK信号系统和mTOR信号通路等途径治愈COVID-19/LUAD合并症。根据集落形成和增殖测定的结果,二甲双胍具有抑制A549细胞增殖的能力。在 A549 细胞中,二甲双胍增加葡萄糖摄取和乳酸生成,同时减少 ATP 合成和 NAD /NADH 比率。综上所述,PTEN和mTOR可能是二甲双胍治疗COVID-19/LUAD的潜在靶点。二甲双胍抑制肺腺癌细胞增殖的机制可能与PI3K/AKT信号通路和mTOR信号通路调控的糖代谢有关。我们的研究为治疗 COVID-19/LUAD 提供了新的理论基础。© 2024。作者。
Lung adenocarcinoma (LUAD) is the most common and aggressive subtype of lung cancer, and coronavirus disease 2019 (COVID-19) has become a serious public health threat worldwide. Patients with LUAD and COVID-19 have a poor prognosis. Therefore, finding medications that can be used to treat COVID-19/LUAD patients is essential. Bioinformatics analysis was used to identify 20 possible metformin target genes for the treatment of COVID-19/LUAD. PTEN and mTOR may serve as hub target genes of metformin. Metformin may be able to cure COVID-19/LUAD comorbidity through energy metabolism, oxidoreductase NADH activity, FoxO signalling pathway, AMPK signalling system, and mTOR signalling pathway, among other pathways, according to the results of bioinformatic research. Metformin has ability to inhibit the proliferation of A549 cells, according to the results of colony formation and proliferation assays. In A549 cells, metformin increased glucose uptake and lactate generation, while decreasing ATP synthesis and the NAD+/NADH ratio. In summary, PTEN and mTOR may be potential targets of metformin for the treatment of COVID-19/LUAD. The mechanism by which metformin inhibits lung adenocarcinoma cell proliferation may be related to glucose metabolism regulated by PI3K/AKT signalling and mTOR signalling pathways. Our study provides a new theoretical basis for the treatment of COVID-19/LUAD.© 2024. The Author(s).