COX-2特异性抑制剂依托考昔对白血病化疗增效作用的体外研究

In vitro study of COX-2 inhibitor, etoricoxibe, for leukemia

目的研究COX-2抑制剂与化疗药物合用对白血病细胞株杀伤作用的影响。方法改良MTT法检测Jurkat、K562、K562／A02白血病细胞株分别用化疗药物多柔比星、柔红霉素、长春新碱、阿糖胞苷、门冬酰胺酶、地塞米松诱导凋亡及联用COX-2特异性抑制剂依托考昔后IC50及药物抑制曲线的改变，金氏方程计算药物联用的增效作用。结果Jurkat、K562及K562／A02细胞株单独加依托考昔时，均未出现生长抑制，Jurkat联用依托考昔及多个浓度的多柔比星、柔红霉素、长春新碱或门冬酰胺时，均比化疗药单独使用时抑制率提高（Q≥1．15）；联用依托考昔及地塞米松时抑制率降低，表现H；拮抗作用（Q〈0．85）；K562联用多个浓度的阿糖胞苷、多柔比星或柔红霉素时，表现出协同作用（Q≥1．15）；K562／A02联用依托考昔及多柔比星时，表现出协同作用（Q≥1．15）。结论COX-2特异性抑制剂依托考昔不能直接抑制白血病细胞，在体外化疗药物作用于白血病细胞株时，加依托考昔表现出增效作用。

Objective To study the effects of COX-2 inhibitor and chemotherapeutic drugs on leukemia cells. Methods MTT assay was used to determine the IC50 of cell lines induced by chemotherapeutic drugs, such as doxorubicin, daunorubicin, vincristine, cytarabine, asparaginase, dexamethasone, and etoricoxib. Results Jurkat, K562, and K562/AO2 leukemia cell lines added etoricoxib and none got growth inhibition. But etoricoxib combined with various concentrations of Doxorubicin（DOX）, daunorubicin（DNR）, vincristine, and asparaginase, the inhibitory rate of them was higher than that of chemotherapy drugs alone （ Q≥1. 15 ） . When etoricoxib added to various concentrations of dexamethasone, the suppression rate decreased, showed antagonism （ Q 〈 0.85 ） . K562 cell line associated with multiple concentrations of cytarabine （Ara-c）, DOX, or DNR, showing a synergistic effect （ Q≥1. 15 ）. K562/AO2 cell lines treated with etoricoxib and DOX, showing a synergistic effect （ Q≥1. 15 ）. Conclusion COX-2 inhibitors may increase the sensitivity of leukemia cells to chemotherapeutic drugs.