Irreversible EGFR inhibitor EKB-569 targets low-LET γ-radiation-triggered rel orchestration and potentiates cell death in squamous cell carcinoma.

ABSTRACT: EKB-569 (Pelitinib), an irreversible EGFR tyrosine kinase inhibitor has shown potential therapeutic efficiency in solid tumors. However, cell-killing potential in combination with radiotherapy and its underlying molecular orchestration remain to be explored. The objective of this study was to determine the effect of EKB-569 on ionizing radiation (IR)-associated NFκB-dependent cell death. SCC-4 and SCC-9 cells exposed to IR (2Gy) with and without EKB-569 treatment were analyzed for transactivation of 88 NFκB pathway molecules, NFκB DNA-binding activity, translation of the NFκB downstream mediators, Birc1, 2 and 5, cell viability, metabolic activity and apoptosis. Selective targeting of IR-induced NFκB by EKB-569 and its influence on cell-fate were assessed by overexpressing (p50/p65) and si

SUBMITTER: Aravindan N 

PROVIDER: S-EPMC3248439 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature