Tipping Growth Inhibition into Apoptosis by Combining Treatment with MDM2 and WIP1 Inhibitors in p53WT Uterine Leiomyosarcoma.

ABSTRACT: As there is no optimal therapeutic strategy defined for women with advanced or recurrent uLMS, there is an urgent need for the discovery of novel, targeted approaches. One such area of interest is the pharmacological inhibition of the MDM2-p53 interaction with small-molecular-weight MDM2 inhibitors. Growth inhibition and cytotoxic assays were used to evaluate uLMS cell line responses to MDM2 inhibitors as single agents and in combination, qRT-PCR to assess transcriptional changes and Caspase-Glo 3/7 assay to detect apoptosis. RG7388 and HDM201 are potent, selective antagonists of the MDM2-p53 interaction that can effectively stabilise and activate p53 in a dose-dependent manner. GSK2830371, a potent and selective WIP1 phosphatase inhibitor, was shown to significantly potentiate the growth

SUBMITTER: Chamberlain V 

PROVIDER: S-EPMC8750798 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature