Abstract: Objective to explore the function of Sirt1 in drug resistance of CML（chronic myelogenous leukemia）K562 cells. Methods K562 cells stably expressing dominate negative Sirt1 (H363Y) or Sirt1 shRNA were treated with H2O2 and etoposide. Cleaved caspase3, Bax and γ-H2A.X signals were detected by Western blotting; MCF-7 and 293A cells overexpressing wild type Sirt1 were treated with H2O2 and etoposide. γ-H2A.X was detected by Western blotting. Results Sirt1-H363Y and Sirt1 shRNA expression in K562 cells could enhance the cleavage of caspase3 and the expression of Bax, but inhibit the formation ofγ-H2A.X induced by H2O2 and etoposide. On the contrary, overexpression of wild type Sirt1 in MCF-7 and 293A cells promotes the formation ofγ-H2A.X. Conclusion Sirt1 could enhance the drug resistance and signal for DNA repair in K562 cells.

Key words: Sirt1, DNA damage, drug resistance, K562 cells