Inhibiting the endoplasmic reticulum stress response enhances the effect of doxorubicin by altering the lipid metabolism of liver cancer cells.

ABSTRACT: Hepatocellular carcinoma (HCC) is characterized by a low and variable response to chemotherapeutic treatments. One contributing factor to the overall pharmacodynamics is the activation of endoplasmic reticulum (ER) stress pathways. This is a cellular stress mechanism that becomes activated when the cell's need for protein synthesis surpasses the ER's capacity to maintain accurate protein folding, and has been implicated in creating drug-resistance in several solid tumors.

Objective

To identify the role of ER-stress and lipid metabolism in mediating drug response in HCC.

Methods

By using a chemically-induced mouse model for HCC, we administered the ER-stress inhibitor 4μ8C and/or doxorubicin (DOX) twice weekly for three weeks post-tumor initiation. Histological analyses were p

SUBMITTER: Kopsida M 

PROVIDER: S-EPMC10755054 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature