A novel small molecule glycolysis inhibitor WZ35 exerts anti-cancer effect via metabolic reprogramming
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Le résumé fourni par la source
BACKGROUND: Liver cancer is the fifth leading cause of cancer death worldwide, but early diagnosis and treatment of liver cancer remains a clinical challenge. How to screen and diagnose liver cancer early and prolong the survival rate is still the focus of researchers. METHODS: Cell experiments were used to detect the effect of WZ35 on the colony formation ability and proliferation activity of hepatoma cells, nude mouse experiment to observe the in vivo anticancer activity and toxic side effects of WZ35; metabolomics analysis, glucose metabolism experiment and Seahorse analysis of liver cancer cells treated with WZ35; cell experiments combined with bioinformatics analysis to explore the mechanism of WZ35-mediated metabolic reprogramming to exert anticancer activity; tissue microarray and case analysis to evaluate the clinical significance of biomarkers for early diagnosis, treatment and prognosis evaluation of liver cancer. RESULTS: WZ35 inhibited the proliferation activity of various cell lines of liver cancer, and showed good therapeutic effect in nude mice model of hepatocellular carcinoma without obvious toxic and side effects; WZ35 inhibited the absorption of glucose in hepatoma cells, and the drug effect glycolysis, phosphorylation and purine metabolism are relatively seriously damaged; WZ35 mainly inhibits YAP from entering the nucleus as a transcription factor activator by activating oxidative stress in liver cancer cells, reducing the transcription of GLUT1, and finally reducing its GLUT1. Tissue microarray and case analysis showed that GLUT1 and YAP were highly expressed and correlated in liver cancer patients, and were associated with poor patient prognosis. The GLUT1-YAP risk model had a high score in predicting prognosis. CONCLUSION: The study confirms that WZ35 is a small molecule glycolysis inhibitor, and through its properties, it mediates metabolic reprogramming dominated by impaired glycolysis, oxidative phosphorylation and purine metabolism to inhibit the proliferation activity of liver cancer cells. Our findings present novel insights into the pathology of liver cancer and potential targets for new therapeutic strategies. GLUT1-YAP has important reference significance for predicting the stages of disease progression in liver cancer patients and have the potential to serve as novel biomarkers for the diagnosis and treatment of liver cancer.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- A novel small molecule glycolysis inhibitor WZ35 exerts anti-cancer effect via metabolic reprogramming
- Date Crossref
- 18/11/2022
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Wenzhou Medical University Laboratory Animal Centre pays non établi dans la noticeUniversité ou école supérieure
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Affiliated Eye Hospital of Wenzhou Medical College pays non établi dans la noticeÉtablissement de santé
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State Key Laboratory of Ophthalmology pays non établi dans la noticeStructure de recherche
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Shanghai Jiao Tong University Department of Endocrine and Metabolic Diseases pays non établi dans la noticeUniversité ou école supérieure
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Ruijin Hospital pays non établi dans la noticeÉtablissement de santé
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Sir Run Run Shaw Hospital pays non établi dans la noticeÉtablissement de santé
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Zhejiang University pays non établi dans la noticeUniversité ou école supérieure
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First Affiliated Hospital of Wenzhou Medical University pays non établi dans la noticeÉtablissement de santé
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Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University pays non établi dans la noticeÉtablissement de santé
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School of Ophthalmology and Optometry pays non établi dans la noticeUniversité ou école supérieure
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College of Medicine Department of Cardiology pays non établi dans la noticeUniversité ou école supérieure
Laboratory Animal Centre — Wenzhou Medical University, Affiliated Eye Hospital of Wenzhou Medical College et State Key Laboratory of Ophthalmology, avec 8 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.