Folate deficiency-triggered redox pathways confer drug resistance in hepatocellular carcinoma

Oncotarget
Chun-Te HoTsan-Zon Liu

Abstract

Patients with hepatocellular carcinoma (HCC) are prone to folate deficiency (FD). Here we showed that, in cell line-specific manner, FD caused resistance to FD-induced oxidative stress and multi-drug resistance (MDR). This resistance was due to upregulation of glucose-regulated protein 78 (GRP78) and Survivin. Using siRNA and Epigallocatechin gallate (EGCG), we found that GRP78 and Survivin cooperatively conferred MDR by decreasing FD-induced ROS generation. Our data showed that FD increases GRP78 and Survivin, which serve as ROS inhibitors, causing MDR in HCC. We suggest that folate supplementation may enhance the efficacy of chemotherapy.

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Citations

Jul 5, 2016·International Journal of Molecular Sciences·Lian-Hua CuiJin-Su Choi
Jun 24, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Kun-Goung LaiChi-Liang Chern
Nov 12, 2020·BMC Gastroenterology·Giulia MalaguarneraMichele Malaguarnera
May 3, 2021·European Journal of Medicinal Chemistry·Meizhu WangWen Zhou

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Methods Mentioned

BETA
nuclear translocation
flowcytometric
protein folding
electrophoresis
ELISA
flowcytometry

Software Mentioned

CellQuest
Sigma plot

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