A Study Of The Effect Of Cyclooxygensae-2 Inhibitor Celecoxib On MDR And Apoptosis In Myelogenous Leukemia

Objective: To study the expression of cyclooxygenase-2(COX-2) in the patients with chronic myelocytic leukemia(CML), and explore the relationship between COX-2 and multidrug resistance gene 1 (MDR-1) in the chronic myelocytic leukemia (K562/ADM) cell line. And to study the effects of selective COX-2 inhibitor celecoxib on proliferation and apoptosis of acute promyelocytic leukemia (NB₄) cell line, and to investigate the feasibility of clinical treatment of leukemia with the selective COX-2 inhibitor.Methods: Expression of COX-2 mRNA and its protein in the patients with CML was detected by reverse transcript polymerase chain reaction (RT-PCR) and western blot assay(westernblot). After treatment of K562/ADM with different doses of celecoxib, inhibition of cell growth was estimated by MTT assay, both COX-2 mRNA and MDR-1 mRNA in K562/ADM was respectively detected by RT-PCR, P170 andrhodamine 123 were separately analysed by flow cytometry. After treatment of NB4 with different doses of celecoxib, the inhibition of NB4 growth was assayed by MTT, and DNA fragmentation was examined by DNA Ladder with 8% Agarose gel. The percentage of apoptotic cells and the change of bcl-2 expression were estimated by flow cytometry.Results: High expression of COX-2 was found in the patients with CML, but not in normal haematopoietic cell. With a doses-related increase of celecoxib, it could effectively inhibit the K562/ADM proliferation, and downregulate the expression of COX-2 and MDR-1, and reduce PI70 expression in K562/ADM. Celecoxib could effectively reduce the expression of bcl-2, which was responsible for the apoptosis inducing in NB4.Conclusion: It is revealed that high expression of COX-2 was found in the patients with CML, as the disease progressing it would become higher. With downregulation of COX-2 by selective cyclooxygenase-2 inhibitor celecoxib, it could effectively reduce the expression of MDR-1 mRNA and PI70 in K562/ADM. Celecoxib could also evidently induce apoptosis in NB4 due to downregulation of bcl-2 protein.