PPARα activator irbesartan suppresses the proliferation of endometrial carcinoma cells via SREBP1 and ARID1A  

作　　者：YU LU TSUTOMU MIYAMOTO HODAKA TAKEUCHI FUMI TSUNODA NAOKI TANAKA TANRI SHIOZAWA 

机构地区：[1]Department of Obstetrics and Gynecology,School of Medicine,Shinshu University,Matsumoto,390-8621,Japan [2]Department of Global Medical Research Promotion,School of Medicine,Shinshu University Graduate,Matsumoto,Nagano,390-8621,Japan [3]International Relations Office,School of Medicine,Shinshu University,Matsumoto,Nagano,390-8621,Japan [4]Research Center for Social Systems,Shinshu University,Matsumoto,Nagano,390-8621,Japan

出　　处：《Oncology Research》2023年第3期239-253,共15页肿瘤学研究（英文）

基　　金：supported by JSPS KAKENHI Grant Number 18K09285.

摘　　要：Endometrial carcinoma(EMC)is associated with obesity;however,the underlying mechanisms have not yet been elucidated.Peroxisome proliferator-activated receptor alpha(PPARα)is a nuclear receptor that is involved in lipid,glucose,and energy metabolism.PPARαreportedly functions as a tumor suppressor through its effects on lipid metabolism;however,the involvement of PPARαin the development of EMC remains unclear.The present study demonstrated that the immunohistochemical expression of nuclear PPARαwas lower in EMC than in normal endometrial tissues,suggesting the tumor suppressive nature of PPARα.A treatment with the PPARαactivator,irbesartan,inhibited the EMC cell lines,Ishikawa and HEC1A,by down-regulating sterol regulatory element-binding protein 1(SREBP1)and fatty acid synthase(FAS)and up-regulating the tumor suppressor genes p21 and p27,antioxidant enzymes,and AT-rich interaction domain 1A(ARID1A).These results indicate the potential of the activation of PPARαas a novel therapeutic approach against EMC.

关 键 词：Peroxisome proliferator-activated receptor alpha Sterol regulatory element-binding protein 1 ANTIOXIDANT Migration 

分 类 号：R737.33[医药卫生—肿瘤]