Suppression of heat shock protein 27 using OGX-427 induces endoplasmic reticulum stress and potentiates heat shock protein 90 inhibitors to delay castrate-resistant prostate cancer.

ABSTRACT:

Background

Although prostate cancer responds initially to androgen ablation therapies, progression to castration-resistant prostate cancer (CRPC) frequently occurs. Heat shock protein (Hsp) 90 inhibition is a rational therapeutic strategy for CRPC that targets key proteins such as androgen receptor (AR) and protein kinase B (Akt); however, most Hsp90 inhibitors trigger elevation of stress proteins like Hsp27 that confer tumor cell survival and treatment resistance.

Objective

We hypothesized that cotargeting the cytoprotective chaperone Hsp27 and Hsp90 would amplify endoplasmic reticulum (ER) stress and treatment-induced cell death in cancer.

Design, setting, and participants

Inducible and constitutive Hsp27 and other HSPs were measured by real-time reverse transcripti

SUBMITTER: Lamoureux F 

PROVIDER: S-EPMC4079118 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature