Dose-and time-dependent effects of selective cyclooxygenase-2 inhibitor NS398 on apoptosis of K562 leukemia cells

【Objective】To observe the mechanism and effect of cyclooxygenase-2 inhibitor NS398 on proliferation and apoptosis of leukemia cell line K562. 【Methods】The various concentrations of NS398 were added into culture media system to induce apoptosis of leukemia cell line K562. The K562 cell inhibition and apoptosis were detected by MTT assay, flow cytometry and comet assay. Western blot analysis was applied to determination of interrelated protein expression in K562 cells.【Results】NS398 inhibited proliferation and induced apoptosis of leukemia cell line K562 in a dose-and timedependent manner. There were singificantly differences among the various concentration groups (P 0.05). NS398 stimulated caspase-3 and caspase-9 expression at protein level in K562 cells, and promoted accumulation of P53 protein, Bax over-expression and Bcl-xL down-expression.【Conclusion】NS398 significantly inhibits the proliferation and induces apoptosis of K562 cells. It can be concluded that NS398 enhances caspase-3 and caspase-9 expression via post-translational regulation, and provides a new mechanism by which specific COX-2 inhibitors suppress proliferation of leukemia cells. Mechanisms of leukemia cell line K562 apoptosis may be involved in accumulation of Bax by p53 expression and up-reugulated caspase-3 and caspase-9.