Quercetin inhibits truncated isoform of dopamine-and cAMP-regulated phosphoprotein as adjuvant treatment for trastuzumab therapy resistance in HER2-positive breast cancer

作     者：Han-Sheng Chang Tzu-Chun Cheng Shih-Hsin Tu Chih-Hsiung Wu You-Cheng Liao Jungshan Chang Min-Hsiung Pan Li-Ching Chen Yuan-Soon Ho 

作者机构：Department of Biological Science&TechnologyCollege of Life SciencesChina Medical UniversityTaichung 406TaiwanChina Institute of Biochemistry and Molecular BiologyCollege of Life SciencesChina Medical UniversityTaichung 406TaiwanChina Department of SurgerySchool of MedicineCollege of MedicineTaipei Medical UniversityTaipei 110TaiwanChina Department of SurgeryTaipei Medical University HospitalTaipei 110TaiwanChina Graduate Institute of Medical SciencesCollege of MedicineTaipei Medical UniversityTaipei 110TaiwanChina Institute of Food Sciences and TechnologyNational Taiwan UniversityTaipei 106TaiwanChina 

出 版 物：《Food Science and Human Wellness》 (食品科学与人类健康（英文）)

年 卷 期：2024年第13卷第5期

页      面：2653-2667页

核心收录：

学科分类：1008[医学-中药学(可授医学、理学学位)] 1006[医学-中西医结合] 100602[医学-中西医结合临床] 10[医学] 

基　　金：The National Science and Technology Council of Taiwan funded this study 

主　　题：p95-Human epidermal growth factor receptor 2 (HER2) HER2-positive breast cancer Quercetin Trastuzumab resistance Truncated isoform of dopamine-and cAMPregulated phosphoprotein 

摘      要：Trastuzumab resistance is one of the causes of poor prognosis in patients with human epidermal growth factor receptor 2(HER2)-positive(HER2+)breast cancer(BC).The truncated isoform of dopamine-and cAMPregulated phosphoprotein(t-DARPP)has been reported to be involved in trastuzumab therapy resistance and promoting tumor *** evaluate the t-DARPP expression in BC,paired tumors and surrounding normal tissues were analyzed by real-time polymerase chain reaction and confirmed higher DARPP-32 kDa family mRNA expression in HER2+BC tumor *** established 2 patient-derived xenografts(PDX)mice models to test the efficacy of trastuzumab,named model 1(non-responder)and model 2(responder).t-DARPP and p95-HER2 protein-protein interactions were detected in PDX tumor tissue from non-responders using Förster resonance energy transfer ***,there is no response from the ***,mechanistic studies using transwell and western blot assays demonstrated that t-DARPP could upregulate epithelial-mesenchymal transition signaling proteins,enhance p95-HER2 expression and promote cell *** found that quercetin effectively reduced t-DARPP expression in HER2+BC *** t-DARPP ShRNA-suppressed cells,quercetin synergistically enhanced trastuzumab-induced apoptotic cell death and G2/M phase *** conclusion,the combination of quercetin and trastuzumab treatment by targeting t-DARPP in HER2+BC patients has the potential as a biomarker for mitigating drug resistance.