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Metformin Increases Survival in Hypopharyngeal Cancer Patients with Diabetes Mellitus: Retrospective Cohort Study and Cell-Based Analysis

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dc.creatorTsou, Yung-An
dc.creatorChang, Wei-Chao
dc.creatorLin, Chia-Der
dc.creatorChang, Ro-Lin
dc.creatorTsai, Ming-Hsui
dc.creatorShih, Liang-Chun
dc.creatorStaniczek, Theresa
dc.creatorWu, Tsu-Fang
dc.creatorHsu, Hui-Ying
dc.creatorChang, Wen-Dien
dc.creatorLai, Chih-Ho
dc.creatorChen, Chuan-Mu
dc.date2021-03
dc.date.accessioned2021-11-11T08:16:40Z
dc.date.accessioned2025-07-27T15:03:23Z
dc.date.available2021-11-11T08:16:40Z
dc.date.issued2021-11-11T08:16:40Z
dc.description.abstractHypopharyngeal squamous cell carcinoma (HSCC) is usually diagnosed at an advanced stage, leading to a poor prognosis. Even after improvement of surgical techniques, chemotherapy, and radiation technology, the survival rate of HSCC remains poor. Metformin, which is commonly used for type 2 diabetes mellitus (DM), has been suggested to reduce the risk of various cancer types. However, only a few clinical studies mentioned the relationship between metformin use and HSCC. Hence, the aim of this study was to elucidate the specific effect and mechanism of action of metformin in hypopharyngeal cancer. We first assessed whether metformin use has an effect on hypopharyngeal cancer patients with DM by conducting a retrospective cohort study. Our results showed that DM hypopharyngeal cancer patients who used metformin exhibited significantly better overall survival rates than that without metformin treatment. The cell-based analysis further indicated that metformin treatment regulated p38/JNK pathway to reduce Cyclin D1 and Bcl-2 expressions. In addition, metformin activated the pathways of AMPK alpha and MEK/ERK to phosphorylate p27(Thr198) and reduce mTOR phosphorylation in cells. These actions direct cells toward G1 cell cycle arrest, apoptosis, and autophagy. Our results, through combining a clinical cohort analysis with an in vitro study, demonstrate that metformin can be used for drug repositioning in the treatment of DM patients with hypopharyngeal cancer.
dc.format.extent103 bytes
dc.format.mimetypetext/html
dc.identifier.issn1424-8247
dc.identifier.urihttps://ir.ntus.edu.tw/handle/987654321/64487
dc.languageen_US
dc.publisherBASEL, SWITZERLAND:MDPI
dc.relationPHARMACEUTICALS, 14(3)
dc.subjecthypopharyngeal squamous cell carcinoma
dc.subjectmetformin
dc.subjectdrug repositioning
dc.subjectanticancer
dc.subjectmortality
dc.subjectautophagy
dc.titleMetformin Increases Survival in Hypopharyngeal Cancer Patients with Diabetes Mellitus: Retrospective Cohort Study and Cell-Based Analysis
dc.typearticle
dspace.entity.typePublication

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