Blocking the JAK2/STAT3 and ERK pathways suppresses the proliferation of gastrointestinal cancers by inducing apoptosis

作     者：Xi WANG Chunyan DAI Yifei YIN Lin WU Weiyang JIN Yufei FU Zhe CHEN Ke HAO Bin LU Xi WANG;Chunyan DAI;Yifei YIN;Lin WU;Weiyang JIN;Yufei FU;Zhe CHEN;Ke HAO;Bin LU

作者机构：Key Laboratory of Digestive Pathophysiology of Zhejiang Provincethe First Affiliated Hospital of Zhejiang Chinese Medical UniversityZhejiang Chinese Medical UniversityHangzhou 310006China College of Life and Environmental SciencesHangzhou Normal UniversityHangzhou 310036China Research Center of Blood Transfusion MedicineMinistry of Education Key Laboratory of Laboratory MedicineDepartment of Blood TransfusionZhejiang Provincial People's HospitalPeople's Hospital of Hangzhou Medical CollegeHangzhou 310014China 

出 版 物：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 (浙江大学学报（英文版）B辑（生物医学与生物技术）)

年 卷 期：2021年第22卷第6期

页      面：492-503页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：the Zhejiang Provincial Natural Science Foundation of China(Nos.LQ18H280005 and LY21H030002) the National Natural Science Foundation of China(Nos.81770535,81600595,81503297,81603340,81773945,and 81803775) the Medical Health Science and Technology Project of Zhejiang Provincial Health Commission(Nos.2019RC228,2019RC229,and 2019RC113) the Open Foundation from Chinese and Western Integrative Medicine in the Most Important Subjects of Zhejiang(No.ZXYJH2018002),China 

主　　题：Gastrointestinal cancers JAK2/STAT3 pathway ERK pathway Crosstalk Apoptosis 

摘      要：Dysregulated crosstalk between different signaling pathways contributes to tumor development,including resistance to cancer *** the present study,we found that the mitogen-activated extracellular signal-regulated kinase(MEK)inhibitor trametinib failed to suppress the proliferation of PANC-1 and MGC803 cells by activating the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway,while the JAK2 inhibitor fedratinib failed to inhibit the growth of the PANC-1 cells upon stimulation of extracellular signal-regulated kinase(ERK)*** particular,the most prominent enhancement of the anti-proliferative effect resulted from the concurrent blockage of the JAK2/STAT3 and ERK signaling ***,the combination of the two inhibitors resulted in a reduced tumor burden in *** evidence suggests novel crosstalk between JAK2/STAT3 and ERK signaling in gastric cancer(GC)and pancreatic ductal adenocarcinoma(PDAC)cells and provides a therapeutic strategy to overcome potential resistance in gastrointestinal cancer.