Effect Of Selinexor Combined With Imatinib On Proliferation And Apoptosis Of K562/G01 Cells

Objective:To observe the effect of Selinexor(SEL)combined with Imatinib(IM)on the proliferation inhibition and the apoptosis of imatinib resistant chronic myeloid leukemia K562/G01(KG)cell line,and explore the possible mechanism.Methods:chronic myeloid leukemia(K562)cells and KG cells were treated with SEL or IM respectively or in combination.Cell viability was examined by MTT assay.Apoptosis was assessed by flow cytometry(FCM).BCR-ABLm RNA was detected by RT-PCR.XPO1 protein was detected by Western blot.Results:1.IM and SEL could both inhibit the proliferation of K562 cells and KG cells and was dose-dependent.IC50 of IM to KG cells(6.48μmol/L)was 40.5 times as large as that of IM to K562 cells(0.16μmol/L).IC50 of SEL to K562/G01 cells(275.9nmol/L)was slightly larger of SEL to K562 cells(132.0nmol/L)。2.Compared with SEL or IM,SEL combined with IM significantly inhibited cell proliferation(had a synergistic effect),induced cell apoptosis,downregulate the levels of BCR-ABLm RNA and inhibit the expessions of XPO1 protein in KG cells.Conclusion:SEL combined with IM can synergistically inhibit the proliferation and induce apoptosis of KG cells,and inhibit the expressions of BCR-ABLm RNA and XPO1 protein to exert anti-leukemia effect.