Combination of celecoxib and doxorubicin increases growth inhibition and apoptosis in acute myeloid leukemia cells
Combination of celecoxib and doxorubicin increases growth inhibition and apoptosis in acute myeloid leukemia cells
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DOI：
10.3109/10428194.2013.781170
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发表时间：
2013-11-01
影响因子：
2.6
通讯作者：
Wang, Cheng-mei
中科院分区：
文献类型：
--
作者：
Chen, Chen;Xu, Wei;Wang, Cheng-mei
环氧合酶-2(COX-2)抑制剂已被证明在多种实体瘤细胞中增强治疗药物的抗肿瘤活性。然而，在血液系统肿瘤中，尤其是在急性髓系白血病(AML)中，这一点还没有得到很好的证实。本研究旨在探讨环氧合酶-2特异性抑制剂塞来昔布与阿霉素联合应用对人白血病细胞生长和凋亡的影响。塞来昔布与阿霉素联合作用可显著抑制急性白血病细胞株HL60和原代AML细胞的生长和诱导细胞凋亡。抑制细胞生长的同时，细胞周期蛋白E和细胞周期蛋白依赖性激酶2(CDK2)的表达下调，这与细胞停滞在G0/G1期有关。伴随着促凋亡作用的是下调凋亡抑制蛋白Survivin的表达，Survivin介导AML细胞的抗凋亡。这些结果首次证明塞来昔布和阿霉素对AML细胞的生长抑制和促凋亡作用是协同的。
Cyclooxygenase-2 (COX-2) inhibitors have been shown to enhance antitumor activity of therapeutic agents in a variety of solid tumor cells. However, this has not been well established in hematopoietic tumors, especially in acute myeloid leukemia (AML). This study was designed to investigate the effects of the combination of celecoxib, a specific COX-2 inhibitor, and doxorubicin on cell growth and apoptosis in human leukemia cells. Co-treatment with celecoxib and doxorubicin significantly inhibited cell growth and induced cell apoptosis in the acute leukemia cell line HL60 and primary AML cells. The growth inhibition effect was accompanied by down-regulation of the expression of cyclin E and cyclin-dependent kinase 2 (CDK2), the key regulators of cell cycle progression, which was associated with arrest of cells at G0/G1 phase. The pro-apoptotic effect was accompanied by down-regulation of the expression of survivin, an inhibitor of apoptosis protein, which mediated anti-apoptosis in AML cells. These results provide the first evidence that the growth inhibitory and pro-apoptotic effects of celecoxib and doxorubicin on AML cells are synergistic.