Konjac glucomannan enhances 5-FU-induced cytotoxicity of hepatocellular carcinoma cells via TLR4/PERK/CHOP signaling to induce endoplasmic reticulum stress

作     者：YONGKANG SHI JUN MA KE CHEN BIN CHEN 

作者机构：Department of General SurgeryCancer CenterDivision of Gastrointestinal and Pancreatic SurgeryZhejiang Provincial People’s HospitalAffiliated People’s HospitalHangzhou Medical CollegeHangzhou310011China 

出 版 物：《Oncology Research》 (肿瘤学研究（英文）)

年 卷 期：2022年第30卷第4期

页      面：201-210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：supported by the Zhejiang Traditional Chinese Medicine Science and Technology Plan Scientific Research(No.2022ZB038) Zhejiang Province Public Welfare Technology Research Program Project(No.GF19H160018) 

主　　题：Konjac glucomannan 5-FU Hepatocellular carcinoma Drug resistance 

摘      要：5-Fluorouracil(5-FU)is a commonly used chemotherapeutic agent for various ***,the drug resistance developed by tumor cells hinders the therapeutic *** glucomannan(KGM)is indicated to sensitize 5-FU-resistant hepatocellular carcinoma(HCC)cells to *** our study,we found that KGM or 5-FU treatment alone did not affect the malignant cell behaviors and endoplasmic reticulum(ER)stress of 5-FU-resistant HCC cells or HepG2/5-FU and Bel-7402/5-FU cells,while cotreatment with KGM and 5-FU significantly facilitated HCC cell apoptosis and ER stress and suppressed cell proliferation potential and migration ***,we explored the underlying mechanism by which KGM induces 5-FU cytotoxicity in HCC *** found that Toll-like receptor 4(TLR4)was downregulated in KGM-and 5-FU-treated HCC ***4 overexpression reversed the KGM and 5-FU cotreatment-induced inhibition of the malignant behaviors of 5-FU-resistant HCC ***,KGM enhanced 5-FU-induced ER stress by inhibiting TLR4 to activate PERK/ATF4/CHOP *** mouse models were established using HepG2/5-FU cells,and KGM was demonstrated to reverse 5-FU resistance in HCC tumors in vivo by suppressing TLR4 to enhance ER stress and activate PERK/ATF4/CHOP *** conclusion,KGM combined with 5-FU treatment significantly promoted apoptosis and reduced cell proliferation,migration and ER stress in 5-FU-resistant HCC cells compared with KGM or 5-FU treatment alone by downregulating TLR4 to activate PERK/ATF4/CHOP signaling.