MDM2 Inhibition Sensitizes Prostate Cancer Cells to Androgen Ablation and Radiotherapy in a p53-Dependent Manner.

ABSTRACT:

Purpose

Increased murine double minute 2 (MDM2) expression, independent of p53 status, is associated with increased cancer-specific mortality for men with prostate cancer treated with radiotherapy. We assessed MI-219, a small molecule inhibitor of MDM2 with improved pharmacokinetics over nutlin-3, for sensitization of prostate cancer cells to radiotherapy and androgen deprivation therapy, a standard treatment option for men with high-risk prostate cancer.

Experimental design

The effect of MDM2 inhibition by MI-219 was assessed in vitro and in vivo with mouse xenograft models across multiple prostate cancer cell lines containing varying p53 functional status.

Results

MDM2 inhibition by MI-219 resulted in dose- and time-dependent p53 activation and decreased clonogenic

SUBMITTER: Feng FY 

PROVIDER: S-EPMC4840291 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature