Increased sensitivity to apoptosis upon endoplasmic reticulum stress-induced activation of the unfolded protein response in chemotherapy-resistant malignant pleural mesothelioma.

ABSTRACT:

Background

Standard treatment for advanced malignant pleural mesothelioma (MPM) is a cisplatin/pemetrexed (MTA) regimen; however, this is confronted by drug resistance. Proteotoxic stress in the endoplasmic reticulum (ER) is a hallmark of cancer and some rely on this stress signalling in response to cytotoxic chemotherapeutics. We hypothesise that ER stress and the adaptive unfolded protein response (UPR) play a role in chemotherapy resistance of MPM.

Methods

In vitro three-dimensional (3D) and ex vivo organotypic culture were used to enrich a chemotherapy-resistant population and recapitulate an in vivo MPM microenvironment, respectively. Markers of ER stress, the UPR and apoptosis were assessed at mRNA and protein levels. Cell viability was determined based on acid phospha

SUBMITTER: Xu D 

PROVIDER: S-EPMC6035279 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature