MDM2 Inhibition in a Subset of Sarcoma Cell Lines Increases Susceptibility to Radiation Therapy by Inducing Senescence in the Polyploid Cells.

ABSTRACT:

Purpose

Inhibition of p53 by amplification of MDM2 is one of the key contributors in the oncogenesis of a subset of soft tissue sarcoma (STS) known as well-/dedifferentiated liposarcoma. A small molecule MDM2 antagonist, nutlin-3, induces the p53 pathway by disrupting the interaction between MDM2 and p53. Radiation therapy is an integral component for treating liposarcoma and induces p53. Based on wild-type TP53 status in liposarcoma, it was investigated whether MDM2 inhibition with irradiation led to enhanced reactivation of p53 and subsequent p53-mediated effects in liposarcoma.

Methods and materials

Clonogenic assays, immunoblotting, flow cytometry/fluorescence-activated cell sorting, and senescence assays were employed in liposarcoma cell lines after co-treatment

SUBMITTER: Das S 

PROVIDER: S-EPMC7136631 | biostudies-literature | 2020 Mar-Apr

REPOSITORIES: biostudies-literature