Arsenic trioxide inhibits proliferation in K562 cells by changing cell cycle and survivin expression

Abstract

To study the mechanisms involved in the inhibition of chronic myeloid leukemic cells (K562) proliferation induced by arsenic trioxide (As₂O₃) and to explore the potential role of Survivin, an inhibitor of apoptosis protein, in the regulation of As₂O₃ induced cell apoptosis, K562 cells were cultured with As₂O₃ of different concentrations. Cells were collected for proliferation analysis by MTT assay. Cell cycle distribution and cell apoptosis were analyzed by flow cytometry. Expression of Survivin protein and mRNA were detected by flow cytometry and RT-PCR, respectively. Our results showed that As₂O₃ (2–10 μmol/L) inhibited K562 cells growth effectively, but it did not induce cells apoptosis significantly. The percentage of K562 cells at G₂/M phase increased in proportion to As₂O₃ concentrations, and the expression of Survivin mRNA and content of Survivin protein was up-regulated accordingly. It is concluded that As₂O₃ inhibited K562 cells growth by inducing cell cycle arrest mainly at G₂/M phase. Over-expression of Survivin gene and protein might be one of the possible mechanisms contributing to K562 cells resistance to As₂O₃-induced apoptosis.

Keywords

arsenic trioxide / K562 / G₂/M cell cycle arrest / Survivin

References

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