EIF3a-PPP2R5A-mediated ATM/ATR dephosphorylation is essential for irinotecan-induced DNA damage response.

ABSTRACT:

Objectives

The individual differences and pervasive resistance seriously hinder the optimization of irinotecan-based therapeutic effectiveness. Eukaryotic translation initiation factor 3a (eIF3a) plays a key role in tumour occurrence, prognosis and therapeutic response. This study focused on the role of eIF3a in irinotecan-induced DNA damage response.

Materials and methods

The cck8 cell viability and clone survival analyses were used to test the regulatory role of eIF3a on irinotecan sensitivity in HT29 and CACO2 cell lines in vitro. This regulatory role was also verified in vivo by conducting subcutaneous xenograft model. Irinotecan-induced DNA damage, cell cycle arrest and apoptosis were tested by flow cytometry analysis, TUNEL staining, western blot and comet assays. The

SUBMITTER: Mei C 

PROVIDER: S-EPMC9055905 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature