Synergistic Depression of Wnt Pathway by Sequential Combination of Decitabine and Idarubicin in Human Myeloid Leukemic Cell Lines,

In the preliminary experiment, we investigated the effect of anti-leukemia drugs (idarubicin, daunorubicin cytarabine, thalidomide, homoharringtonine) in combination with decitabine of inhibiting growth of myeloid leukemic cell lines. The result showed notable synergistic effect of sequential combination of decitabine and idarubicin. In searching the associated mechanism, we assessed the effect of sequential combination of decitabine and idarubicin in apoptosis, cell cycle arrest, and depression of wnt pathway. Methods: Myeloid leukemia cells (U937, HEL and SKM-1) were treated with decitabine alone, idarubicin alone, and decitabine sequential with idarubicin to determine their impact on cellular proliferation, cell cycle regulation, apoptosis and the regulation of wnt pathway by detecting DNA methylation status, mRNA level and protein expression. Results: The sequential combination of decitabine and idarubicin produced synergistic inhibition of myeloid leukemia cells growth by apoptosis and cell cycle arrest. Sequential treatment with both agents induced synergistic effect on decreasing methylation status of wnt antagonists (SFRP1, HDPR1 and DKK3) which result in re-expression or up-expression of these genes. Furthermore, we found that the down-steam genes of wnt pathway including c-myc and β-catenin were down-regulated. Conclusion: Taken together, these findings showed that decitabine sequentially combined with idarubicin has synergistic anti-leukemia effect, which suggest clinical potential in the treatment of myeloid leukemias.

No relevant conflicts of interest to declare.