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

DOI record: { "DOI": "10.1038/s41598-024-63081-0", "ISSN": [ "2045-2322" ], "URL": "http://dx.doi.org/10.1038/s41598-024-63081-0", "abstract": "<jats:title>Abstract</jats:title><jats:p>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<jats:sup>+</jats:sup>/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.</jats:p>", "alternative-id": [ "63081" ], "article-number": "12406", "assertion": [ { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Received", "name": "received", "order": 1, "value": "13 March 2024" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Accepted", "name": "accepted", "order": 2, "value": "24 May 2024" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "First Online", "name": "first_online", "order": 3, "value": "30 May 2024" }, { "group": { "label": "Competing interests", "name": "EthicsHeading" }, "name": "Ethics", "order": 1, "value": "The authors declare no competing interests." } ], "author": [ { "affiliation": [], "family": "Hou", "given": "Yongwang", "sequence": "first" }, { "affiliation": [], "family": "Yang", "given": "Zhicong", "sequence": "additional" }, { "affiliation": [], "family": "Xiang", "given": "Baoli", "sequence": "additional" }, { "affiliation": [], "family": "Liu", "given": "Jiangmin", "sequence": "additional" }, { "affiliation": [], "family": "Geng", "given": "Lina", "sequence": "additional" }, { "affiliation": [], "family": "Xu", "given": "Dandan", "sequence": "additional" }, { "affiliation": [], "family": "Zhan", "given": "Minghua", "sequence": "additional" }, { "affiliation": [], "family": "Xu", "given": "Yuhuan", "sequence": "additional" }, { "affiliation": [], "family": "Zhang", "given": "Bin", "sequence": "additional" } ], "container-title": "Scientific Reports", "container-title-short": "Sci Rep", "content-domain": { "crossmark-restriction": false, "domain": [ "link.springer.com" ] }, "created": { "date-parts": [ [ 2024, 5, 30 ] ], "date-time": "2024-05-30T03:51:11Z", "timestamp": 1717041071000 }, "deposited": { "date-parts": [ [ 2024, 5, 30 ] ], "date-time": "2024-05-30T04:15:19Z", "timestamp": 1717042519000 }, "funder": [ { "award": [ "20220596" ], "name": "Hebei Health hScientific Research Foundation Project" } ], "indexed": { "date-parts": [ [ 2024, 5, 31 ] ], "date-time": "2024-05-31T00:30:47Z", "timestamp": 1717115447478 }, "is-referenced-by-count": 0, "issue": "1", "issued": { "date-parts": [ [ 2024, 5, 30 ] ] }, "journal-issue": { "issue": "1", "published-online": { "date-parts": [ [ 2024, 12 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "tdm", "delay-in-days": 0, "start": { "date-parts": [ [ 2024, 5, 30 ] ], "date-time": "2024-05-30T00:00:00Z", "timestamp": 1717027200000 } }, { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2024, 5, 30 ] ], "date-time": "2024-05-30T00:00:00Z", "timestamp": 1717027200000 } } ], "link": [ { "URL": "https://www.nature.com/articles/s41598-024-63081-0.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://www.nature.com/articles/s41598-024-63081-0", "content-type": "text/html", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://www.nature.com/articles/s41598-024-63081-0.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "297", "original-title": [], "prefix": "10.1038", "published": { "date-parts": [ [ 2024, 5, 30 ] ] }, "published-online": { "date-parts": [ [ 2024, 5, 30 ] ] }, "publisher": "Springer Science and Business Media LLC", "reference": [ { "DOI": "10.1016/j.ccell.2021.09.003", "author": "H Hu", "doi-asserted-by": "publisher", "first-page": "1531", "journal-title": "Cancer Cell", "key": "63081_CR1", "unstructured": "Hu, H. et al. 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