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探索果糖代谢作为胰腺癌的一种潜在治疗方法。

Exploring fructose metabolism as a potential therapeutic approach for pancreatic cancer.

作者信息

Wang Chengqiang, Wang Lu, Zhao Qing, Ma Jiao, Li Yitao, Kuang Junliang, Yang Xintong, Bi Huichang, Lu Aiping, Cheung Kenneth C P, Melino Gerry, Jia Wei

机构信息

Chinese Medicine Phenome Research Centre, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.

Department of Pharmacology and Pharmacy, University of Hong Kong, Hong Kong, China.

出版信息

Cell Death Differ. 2024 Dec;31(12):1625-1635. doi: 10.1038/s41418-024-01394-3. Epub 2024 Oct 15.

Abstract

Excessive fructose intake has been associated with the development and progression of pancreatic cancer. This study aimed to elucidate the relationship between fructose utilization and pancreatic cancer progression. Our findings revealed that pancreatic cancer cells have a high capacity to utilize fructose and are capable of converting glucose to fructose via the AKR1B1-mediated polyol pathway, in addition to uptake via the fructose transporter GLUT5. Fructose metabolism exacerbates pancreatic cancer proliferation by enhancing glycolysis and accelerating the production of key metabolites that regulate angiogenesis. However, pharmacological blockade of fructose metabolism has been shown to slow pancreatic cancer progression and synergistically enhance anti-tumor capabilities when combined with anti-angiogenic agents. Overall, targeting fructose metabolism may prove to be a promising therapeutic approach in the treatment of pancreatic cancer.

摘要

过量摄入果糖与胰腺癌的发生和发展有关。本研究旨在阐明果糖利用与胰腺癌进展之间的关系。我们的研究结果表明,胰腺癌细胞具有很高的利用果糖的能力,除了通过果糖转运体GLUT5摄取果糖外,还能够通过AKR1B1介导的多元醇途径将葡萄糖转化为果糖。果糖代谢通过增强糖酵解和加速调节血管生成的关键代谢物的产生,加剧了胰腺癌的增殖。然而,果糖代谢的药理学阻断已被证明可减缓胰腺癌的进展,并在与抗血管生成药物联合使用时协同增强抗肿瘤能力。总体而言,靶向果糖代谢可能被证明是治疗胰腺癌的一种有前景的治疗方法。

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