Bromodomain4 inhibitor JQ1 inhibits the proliferation of Ph positive acute lymphocytic leukemia cells and its mechanism / 白血病·淋巴瘤

ABSTRACT

Objective To observe the effect of bromodomain4 (brd4) inhibitor JQ1 on proliferation inhibition and apoptosis of Ph positive acute lymphocytic leukemia (Ph+ ALL) cells, and to explore the influence on the expression of brd4 and its downstream genes (myc and p53), and the reverse effect on bcr-abl.Methods Different concentrations of JQ1 were used on SUP-B15 cells.The proliferation inhibition rate was detected by MTT, the apoptosis rate was determined by flow cytometry (FCM), and the expressions of bcr-abl mRNA, brd4 mRNA, myc mRNA and p53 mRNA were detected by real-time fluorescent quantitative PCR (RT-PCR).Results Different concentrations of JQ1 inhibited SUP-B15 cells proliferation and induced cell apoptosis.The apoptosis rate was significantly increased compared with that in control group with a time-dose dependent manner.Median inhibitory concentration at 72 h was 1.0 pmol/L.At the same time, JQ1 decreased the transcription levels of bcr-abl mRNA, brd4 mRNA and myc mRNA, and increased the transcription level of p53 mRNA.Conclusions As a brd4 inhibitor, JQ1 can decrease the expression of brd4 to affect the expression of its downstream genes myc and p53, meanwhile, it can change the over expression of bcr-abl to suppress the proliferation of Ph+ ALL cells and induce apoptosis.