Metochalcone induces senescence-associated secretory phenotype via JAK2/STAT3 pathway in breast cancer  

作　　者：JIANBO ZHOU FENG WAN BIN XIAO XIN LI CHENG PENG FU PENG 

机构地区：[1]Department of Pharmacology,West China School of Pharmacy,Sichuan University,Chengdu,China [2]State Key Laboratory of Southwestern Chinese Medicine Resources,Chengdu University of Traditional Chinese Medicine,Chengdu,China [3]Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry,Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology,Sichuan University,Chengdu,China [4]Chengdu No.1 Pharmaceutical Co.,Ltd.,Pengzhou,China [5]Chengdu Push Bio-Technology Co.,Ltd.,Chengdu,China

出　　处：《Oncology Research》2024年第5期943-953,共11页肿瘤学研究（英文）

基　　金：funded by the National Natural Science Foundation of China(82003879);Project of Science and Technology Department of Sichuan Province(2023NSFSC1928,2023NSFSC1992);Young Elite Scientists Sponsorship Program China Association for Science and Technology(CACM-2020-QNRC1-01);Project of State Administration of Traditional Chinese Medicine of China(ZYYCXTD-D-202209);Project of Undergraduate Training Programs for Innovation and Entrepreneurship(S202310610637);the Open Research Fund of State Key Laboratory of Southwestern Chinese Medicine Resources(SKLTCM202205).

摘　　要：Breast and lung cancers are the leading causes of mortality and most frequently diagnosed cancers in women and men,respectively,worldwide.Although the antitumor activity of chalcones has been extensively studied,the molecular mechanisms of isoliquiritigenin analog 2',4',4-trihydroxychalcone(metochalcone;TEC)against carcinomas remain less well understood.In this study,we found that TEC inhibited cell proliferation of breast cancer BT549 cells and lung cancer A549 cells in a concentration-dependent manner.TEC induced cell cycle arrest in the S-phase,cell migration inhibition in vitro,and reduced tumor growth in vivo.Moreover,transcriptomic analysis revealed that TEC modulated the activity of the JAK2/STAT3 and P53 pathways.TEC triggered the senescence-associated secretory phenotype(SASP)by repressing the JAK2/STAT3 axis.The mechanism of metochalcone against breast cancer depended on the induction of SASP via deactivation of the JAK2/STAT3 pathway,highlighting the potential of chalcone in senescence-inducing therapy against carcinomas.

关 键 词：Metochalcone Breast cancer Lung cancer SASP JAK2/STAT3 

分 类 号：R730.5[医药卫生—肿瘤]