Blocking Cyclin-Dependent Kinase 4/6 During Single Dose Versus Fractionated Radiation Therapy Leads to Opposite Effects on Acute Gastrointestinal Toxicity in Mice.

ABSTRACT:

Purpose

The delivery of radiation therapy to cure gastrointestinal (GI) cancers is often limited by normal tissue toxicity of the GI tract. Studies using genetically engineered mice have demonstrated an essential role of the cyclin-dependent kinase inhibitor p21 in protecting against GI acute radiation syndrome (GI-ARS). Here, we examined the impact of the Food and Drug Administration-approved, selective, cyclin-dependent kinase 4/6 inhibitor palbociclib (PD-0332991) on the development of GI-ARS induced by single-dose versus fractionated radiation in mice.

Methods and materials

For the single-dose radiation study, C57BL/6J mice were treated with palbociclib or vehicle 28 and 4 hours before subtotal body irradiation (SBI). For the fractionated radiation study, C57BL/6J mice w

SUBMITTER: Lee CL 

PROVIDER: S-EPMC6348051 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature