Affordable Access

deepdyve-link
Publisher Website

Rab27B enhances drug resistance in hepatocellular carcinoma by promoting exosome-mediated drug efflux.

Authors
  • Li, Rui1
  • Dong, Chengyong1
  • Jiang, Keqiu1
  • Sun, Rui1
  • Zhou, Yang2
  • Yin, Zeli1, 3
  • Lv, Jiaxin4
  • Zhang, Junlin1
  • Wang, Qi5
  • Wang, Liming1
  • 1 Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China. , (China)
  • 2 Liaoning Clinical Research Center for Lung Cancer, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China. , (China)
  • 3 Engineering Research Center for New Materials and Precision Treatment Technology of Malignant Tumors Therapy, Dalian Medical University, Dalian, Liaoning, China. , (China)
  • 4 Department of Anesthesiology, The First Affiliated Hospital of Dalian Medical University, Zhongshan Road, Dalian, Liaoning, China. , (China)
  • 5 Department of Respiratory Medicine, The Second Hospital, Dalian Medical University, Dalian, Liaoning, China. , (China)
Type
Published Article
Journal
Carcinogenesis
Publisher
Oxford University Press
Publication Date
Nov 13, 2020
Volume
41
Issue
11
Pages
1583–1591
Identifiers
DOI: 10.1093/carcin/bgaa029
PMID: 32390047
Source
Medline
Language
English
License
Unknown

Abstract

Liver cancer is a major threat to human life and health, and chemotherapy has been the standard non-surgical treatment for liver cancer. However, the emergence of drug resistance of liver cancer cells has hindered the therapeutic effect of chemical drugs. The discovery of exosomes has provided new insights into the mechanisms underlying tumour cell resistance. In this study, we aimed to determine the proteins associated with drug resistance in tumour cells and to elucidate the underlying mechanisms. We found that Rab27B expression in drug (5-fluorouracil, 5Fu)-resistant Bel7402 (Bel/5Fu) cells increased significantly compared with that in drug-sensitive Bel7402 cells. In addition, Bel/5Fu cells secreted more exosomes under 5Fu stimulation. The number of exosomes secreted by Bel/5Fu cells significantly reduced after knocking down Rab27B, and the cellular concentration of 5Fu increased, enhancing its therapeutic effect. We also found that the administration of classical drug efflux pump (P-glycoprotein, P-gp) inhibitors together with knockdown of Rab27B further improved the therapeutic effects of chemotherapy drugs. In conclusion, our findings suggest that Rab27B could be a new therapeutic target in liver cancer. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]

Report this publication

Statistics

Seen <100 times