塞来昔布对人白血病细胞株HL-60细胞增殖及凋亡的影响及其作用机制

本研究旨在探讨塞来昔布（celecoxib）对人急性髓系白血病细胞株HL-60细胞增殖、凋亡的影响及其可能的作用机制。不同浓度塞来昔布作用于HL-60细胞24h后，CCK-8法测定细胞增殖活性，流式细胞技术分析细胞凋亡及细胞周期分布的变化，定量RT—PCR的方法检测细胞周期蛋白DJ、EI及COX-2mRNA的表达。结果表明，不同浓度塞来昔布作用于HL-60细胞24h后，细胞增殖明显受抑，且呈-定的浓度依赖性（r=0．955），24h的IC50值为63．037μmol／L。塞来昔布可诱导HL-60细胞的凋亡，也呈剂量依赖性（r=0．988）。塞来昔布可使HL-60细胞明显阻滞于G0／G1期，可下调cyclinD1、cyclinE1mRNA的表达。塞来昔布可使细胞COX-2mRNA表达水平降低。结论：塞来昔布呈浓度依赖性抑制HL-60细胞增殖，并可能通过下调cyclinD1、cyclinE1的表达引起细胞G0／G1，期阻滞，下调COX-2的表达诱导细胞凋亡。

Effect of COX-2 Inhibitor Celecoxib on Proliferation,Apoptosis of HL-60 Cells and Its Mechanism

This study was aimed to investigate the effect of COX-2 inhibitor celecoxib on proliferation, apoptosis of human acute myeloid leukemia cell line HL-60 and its mechanism. HL-60 cells were cultured with different concentrations of celecoxib for 24 h. Cell proliferation was analyzed by CCK-8 assay, cell apotosis and cell cycle distribution were detected by flow cytometry. Cyclin D1, cyclin E1 and COX-2 mRNA expressions were determined by RT-PCR. The resuits showed that after the HL-60 cells were treated with different concentrations of celecoxib for 24 h, the cell growth was significantly inhibited in a dose-dependent manner（ r = 0. 955 ）, IC50 was 63. 037 μmol/L of celecoxib. Celecoxib could effectively induce apoptosis in HL-60 cells also in dose-dependent manner（ r =0. 988）, blocked the HL-60 cells in the G0/G1 phase. The expression of cyclin D1, cyclin E1 and COX-2 mRNA were dowuregulated. It is concluded that celecoxib can inhibit the proliferation of HL-60 cells in dose-dependent manner, celecoxib causes cell G0/G1 arrest and induces cell apoptosis possibly through down-regulation of the cyclin D1 and cyclin E1 expression, and down-regulation of COX-2 expression respectively.