Apple polyphenol phloretin inhibits typeⅡglucose transporter and enhances anti-HER2 antibody drug binding as an adjuvant treatment for HER2-positive breast cancer  

作　　者：Han-Sheng Chang Tzu-Chun Cheng Shih-Hsin Tu Pei-Han Liao Yu-Ching Lee Chi-Tang Ho Min-Hsiung Pan Li-Ching Chen Yuan-Soon Ho 

机构地区：[1]Department of Biological Science&Technology,College of Life Sciences,China Medical University,Taichung 404,Taiwan,China [2]Institute of Biochemistry and Molecular Biology,College of Life Sciences,China Medical University,Taichung 404,Taiwan,China [3]Department of Surgery,School of Medicine,College of Medicine,Taipei Medical University,Taipei 11031,Taiwan,China [4]Research Center of Cancer Translational Medicine,Taipei Medical University,Taipei 11031,Taiwan,China [5]Department of Food Science,Rutgers University,New Jersey 08901,USA [6]Institute of Food Sciences and Technology,National Taiwan University,Taipei 10617,Taiwan,China

出　　处：《Food Science and Human Wellness》2025年第4期1264-1280,共17页食品科学与人类健康(英文)

基　　金：supported by the Science and Technology Council,Taiwan,China(NSTC 112-2320-B-039-057 and MOST 111-2320-B-039-067-MY3);the China Medical University,Taiwan,China(CMU112-S-18),awarded to Yuan-Soon Ho;the China Medical University,Taiwan,China(CMU112-N-02),awarded to Li-Ching Chen;the Science and Technology Council,Taiwan,China(MOST 110-2320B-039-079)。

摘　　要：This study presents novel findings on the potential of phloretin,an apple polyphenol,to enhance the effectiveness of anti-human epidermal growth factor receptor-2(HER2)antibody therapy in HER2-positive breast cancer patients.Our research reveals that phloretin inhibits typeⅡglucose transporter(GLUT2)activity,significantly reducing cancer cell glucose uptake.We confirmed the overexpression of GLUT1 and GLUT2 mRNA in paired human breast tumor tissues,with GLUT2 overexpression associated explicitly with poorer survival rates in breast cancer patients.Treatment with phloretin was observed to increase the interaction between GLUT2 and HER2 proteins,attenuate glycolysis,and enhance the binding affinity of anti-HER2 antibody drugs to target human breast cancer cells.Furthermore,the efficacy of the combination therapy involving phloretin and antibody drugs was reaffirmed in a cell-derived xenograft tumor animal model,particularly in suppressing the growth of trastuzumab-resistant HER2-positive(HER2+)breast cancer.These significant findings suggest that targeting GLUT2 activity with phloretin in combination with anti-HER2 antibody drugs may help mitigate the development of drug-resistant breast cancer,offering valuable insights for enhancing tumor treatment strategies and contributing to developing more effective therapies.

关 键 词：TypeⅡglucose transporter(GLUT2) PHLORETIN Human epidermal growth factor receptor 2-intracellular domain(HER2-ICD) TRASTUZUMAB Trastuzumab-resistance 

分 类 号：R737.9[医药卫生—肿瘤] TS201.4[医药卫生—临床医学]