Home HOME Neoplasma 2015 Neoplasma Vol.62, No.2, p.180-190, 2015

Journal info

6 times a year.
Founded: 1954
ISSN 0028-2685
ISSN 1338-4317 (online)

Published in English

Editorial Info
Abstracted and Indexed
Submission Guidelines

Select Journal

Webshop Cart

Your Cart is currently empty.

Info: Your browser does not accept cookies. To put products into your cart and purchase them you need to enable cookies.

Neoplasma Vol.62, No.2, p.180-190, 2015

Title: The endoplasmic reticulum stress response is associated with insulin resistance-mediated drug resistance in HepG2 cells
Author: L. LI, G. LI, H. WEI, J. SUN, J. CHEN, B. XIE, B. WANG, J. GU, C. LI, B. TIAN, F. WANG

Abstract: Insulin resistance has a close relationship with tumorigenesis, tumor progression, and cancer prognosis. Importantly, the liver is the main target tissue of insulin, and the resistance to chemotherapeutic agents has been reported in hepatocarcinoma. However, little is known about the relationship between drug resistance and insulin resistance in hepatocarcinoma. Therefore, we treated HepG2 cells (a human hepatoma cell line) with high concentrations of insulin to establish a cell-based model of insulin resistance (HepG2/IR cells) to define the relationship between insulin resistance and the resistance to chemotherapy. We identified that HepG2/IR cells exhibited stable insulin resistance, with decreased glucose consumption, reduced glycogen synthesis, and decreased expression of the insulin receptor gene. HepG2/IR cells also exhibited endoplasmic reticulum (ER) dilatation and degranulation. Molecular markers of endoplasmic reticulum stress, including glucose-regulated protein78 (GRP78) and phosphorylated protein kinase R-like ER kinase (p-PERK), increased significantly, which was accompanied by increased reactive oxygen metabolism and decreased mitochondrial membrane potential. In addition, HepG2/IR cells were resistant to the chemotherapy agent Adriamycin, which was accompanied by the upregulation of multidrug resistance gene 1/ P-glycoprotein (P-gp; an endoplasmic reticulum chaperone that plays a role in ER stress), and enhanced drug efflux. These data suggest that the endoplasmic reticulum (ER) stress response was active in HepG2/IR cells, and that insulin resistance was related to drug resistance in HepG2 cells. Interestingly, the ER stress and chemotherapy resistance observed in HepG2/IR cells could be reversed by treatment with the insulin sensitizer pioglitazone. Therefore, our study suggests that there is a close relationship between the resistance to chemotherapy and insulin resistance in HepG2 cells, and that the ER stress response play a role in insulin resistance-mediated drug resistance in hepatocarcinoma cells.

Keywords: Insulin resistance, drug resistance, P-gp, endoplasmic reticulum stress, HepG2 cells
Published online: 12-Dec-2014
Year: 2015, Volume: 62, Issue: 2 Page From: 180, Page To: 190

download file

© AEPress s.r.o
Copyright notice: For any permission to reproduce, archive or otherwise use the documents in the ELiS, please contact AEP.