[Inducing apoptosis and reversal effect of nilotinib in combination with tetrandrine on multidrug resistance of K562/A02 cell line].
2011
This study was aimed to investigate the relevance of nilotinib in combination with tetrandrine(Tet) on reversing multidrug resistance and inducing apoptosis of K562/A02 cell line and its mechanism.Methyl-thiazol tetrazolium(MTT) assay was employed to examine the pharmacological effect of nilotinib or Tet alone on K562/A02 cell line,the IC50 of daunorubicin(DNR) on K562/A02 cell line treated with nilotinib and Tet was calculated;the flow cytometry(FCM) was employed to detect the apoptosis rate of K562/A02.The expression of bax/survivin mRNA was determined by RT-PCR,and the expression of bax/survivin protein was assayed by Western blot.The results showed that after being treated by 5 nmol/L nilotinib or 1.0 μml/L Tet for 48 hours,IC50 of DNR to K562/A02 was 5.71±0.72 mg/L or 6.52±0.43 mg/L,respectively,while in their combined treatment,IC50 decreased to 3.12±0.13 mg/L.Nilotinib or Tet alone could increase DNR-inducing apoptosis rate of K562/A02 cell,while the apoptosis rate of K562/A02 increased remarkably in combination treatment of nilotinib with Tet.After being treated with 5 nmol/L nilotinib or 1.0 μml/L Tet alone for 48 hours,the expressions of bax mRNA and BAX protein was up-regulated,while both effects were more obvious in combination treatment of nilotinib with Tet.Treatment with 5 nmol/L nilotinib or 1.0 μmol/L Tet alone for 48 hours down-regulated the expression of survivin mRNA and its protein,while treatment of nilotinib in combination with Tet had more significant effect on down-regulation of their expression.It is concluded that the K562/A02 cells are resistant to DNR,nilotinib or Tet alone both can partially reverse resistance of K562/A02 cells to DNR,increase the apoptosis rate of K562/A02 cells.Combination of nilotinib with Tet shows obvious synergistic action,mechanism of which may associate with up-regulation of bax mRNA and BAX protein expressions and down-regulation of survivin mRNA and its protein expressions.
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