Abstract

The study was aimed to investigate the possible mechanism of Notch1 pathway in apoptosis of Ph(+) human ALL Cells(SUP-B15 cells) induced by bromodomain inhibitors JQ1. The SUP-B15 cells were treated with different concentrations of JQ1 for different times. The cell proliferation was analyzed with cytotoxicity test(MTT method). Cell cycle was detected by fluorescence microscopy and flow cytometry. The mRNA expression of MIS2, Notch1, Hes1, BCR-ABL in Notch1 pathway was detected by real-time quantitative PCR. JQ1 0-4 µmol/L could significantly inhibit the viability of SUP-B15 cells treated in does-and time-dependent manner. After SUP-B15 cells were treated with 1,2,4 µmol/L JQ1 for 48 h, the JQ1 could induce S cycle arrest in does-dependent manner which was statistical different from the control at the same time (P<0.05). MIS2, Notch1, Hes1, BCR-ABL mRNA expression was down-regulated by JQ1 which was statistical different from the control (P<0.05). The JQ1 can effectively inhibit the growth and proliferation of SUP-B15 cells and the Notch1 pathway may be one of the important apoptosis mechanisms in Ph(+) ALL cells induced by JQ1.

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