首页|Carfilzomib activates ER stress and JNK/p38 MAPK signaling to promote apoptosis in hepatocellular carcinoma cells

Carfilzomib activates ER stress and JNK/p38 MAPK signaling to promote apoptosis in hepatocellular carcinoma cells

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Hepatocellular carcinoma(HCC)is one of the most prevalent and deadly cancers in the world,which is frequently diagnosed at a late stage.HCC patients have a poor prognosis due to the lack of an efficacious therapeutic strategy.Approved drug repurposing is a way for accelerating drug discovery and can significantly reduce the cost of drug development.Carfilzomib(CFZ)is a second-generation proteasome inhibitor,which is highly efficacious against multiple myeloma and has been reported to possess potential antitumor activities against multiple cancers.However,the underlying mechanism of CFZ on HCC is still unclear.Here,we show that CFZ inhibits the proliferation of HCC cells through cell cycle arrest at the G2/M phase and suppresses the migration and invasion of HCC cells by inhibiting epithelial-mesenchymal transition.We also find that CFZ promotes reactive oxygen species production to induce endoplasmic reticulum(ER)stress and activate JNK/p38 MAPK signaling in HCC cells,thus inducing cell death in HCC cells.Moreover,CFZ significantly inhibits HCC cell growth in a xenograft mouse model.Collectively,our study elucidates that CFZ impairs mitochondrial function and activates ER stress and JNK/p38 MAPK signaling,thus inhibiting HCC cell and tumor growth.This indicates that CFZ has the potential as a therapeutic drug for HCC.

hepatocellular carcinomacarfilzomibER stressJNK/p38 MAPK signalingproteasome inhibitor

Yao Deng、Yujie Li、Mingyue Yang、Yang Gao、Xuling Luo、Hanbin Chen、Meng Guo、Xuefeng Yang、Yongzhang Liu、Jun He、Bin Lu、Naxin Liu

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Department of Gastroenterology and Hunan Provincial Clinical Research Center for Metabolic Associated Fatty Liver Disease,The Affiliated Nanhua Hospital and Department of Cell Biology and Genetics,School of Basic Medical Sciences,Hengyang Medical School,University of South China,Hengyang 421001,China

School of Laboratory Medicine and Life Sciences,Wenzhou Medical University,Wenzhou 325035,China

Department of Gastrointestinal Surgery,The First Affiliated Hospital,Wenzhou Medical University,Wenzhou 325000,China

School of Public Health,Fudan University,Shanghai 200032,China

Department of Oncology,The First Affiliated Hospital,Wenzhou Medical University,Wenzhou 325000,China

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国家自然科学基金国家自然科学基金Special Funding for the Construction of Innovative Provinces in Hunan ProvinceProject of Wenzhou Science and TechnologyProject of Wenzhou Science and TechnologyProject of Wenzhou Science and TechnologyZhejiang Medical and Health Platform Project(Key Talents)Zhejiang Provincial Health Department Medical Support Discipline-Nutrition

31771534315707722021SK4031Y20190206Y2020178Y202101842014RCA01411-ZC24

2024

10.3724/abbs.2024040

生物化学与生物物理学报(英文版)
中国科学院上海生物化学研究所

生物化学与生物物理学报(英文版)

CSTPCD
影响因子：0.772
ISSN：1672-9145
年,卷(期)：2024.56(5)
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