This document discusses a study aiming to elucidate the mechanism by which the HDAC inhibitor Apicidin induces expression of the drug efflux pump P-glycoprotein (P-gp), which may lead to multidrug resistance. The study found that Apicidin treatment activated the PI3K pathway, leading to phosphorylation of the transcription factor SP1. Phosphorylated SP1 then signals chromatin remodeling and activation of the P-gp promoter. This occurred independently of changes in DNA methylation and required the Y-box and GC box regions of the promoter. Blocking the PI3K pathway prevented Apicidin-induced P-gp expression.