塞莱昔布对急性白血病原代细胞增殖、凋亡及促血管新生因子表达的影响  

Effects of celecoxib on proliferation,apoptosis and angiogenesis factors of primary cells of acute leukemia

作　　者：张彦芳[1,2] 阮林海[2] 赵小强[2] 王瑞丽[3] 葛晓华[2] 

机构地区：[1]洛阳职业技术学院内科教研室,河南省471003 [2]河南科技大学第一附属医院血液科 [3]河南科技大学第一附属医院检验科

出　　处：《江苏医药》2013年第9期1009-1012,F0002,共5页Jiangsu Medical Journal

基　　金：河南省卫生厅科技攻关项目(201003081)

摘　　要：目的探讨选择性环氧化酶2(COX-2)抑制剂塞莱昔布对急性白血病(AL)原代细胞增殖、凋亡及促血管新生因子表达的影响。方法收集30例初诊AL患者骨髓单个核细胞标本进行原代细胞培养,加入浓度为20、40、60、80、100、120μmol/L的塞莱昔布培养24、48、72h后,采用MTT法测定细胞生长抑制率,流式细胞仪检测细胞凋亡率,RT-PCR测定80μmol/L塞莱昔布作用48h前后促血管新生因子(VEGF、b-FGF、TGF-β)mRNA的表达。结果不同浓度塞莱昔布作用后,细胞增殖均受到明显抑制,呈剂量和时间依赖性。同一时点不同浓度和同一浓度不同时点的塞莱昔布对AL细胞增殖的抑制率均有统计学差异(P<0.05)。与对照组的凋亡率(3.98±0.6)%相比,40、60、80μmol/L塞莱昔布作用24h后凋亡率明显增高,分别为(8.1±0.9)%、(10.97±1.4)%、(19.78±2.3)%,呈剂量依赖性(P<0.01),VEGF、b-FGF和TGF-βmRNA表达水平显著降低(P<0.01)。结论塞莱昔布能有效抑制AL原代细胞的增殖并诱导其凋亡;其作用可能与下调促血管新生因子表达以抑制血管新生有关。Objective To explore the effects of selective cycloxegenase-2 （COX-2） inhibitor celecoxib on the proliferation, apoptosis and angiogenesis factors of primary cells of acute leukemia （AL）. Methods Mononuclear cells from 30 AL patient were collected and incubated with different concentrations of celecoxib 20,40,60,80,100 and 120 μmol/L for 24,48 and 72 h. The inhibitory and apoptosis rates were detected by MTT and flow cytometry, respectively. The mRNA expressions of angiogenesis factors （VEGF, b-FGF and TGF-β） were detected by RT-PCR after incubated with celecoxib 80/μmol/L for 48 h. Results The cell proliferation decreased significantly in the dose- and time-dependent manners. The inhibitory rate of AL primary cells among in a same concentration and at different time points of celecoxib, or in different concentrations at same time point, was statistically different （P〈0.05）. Compared with control group, the apoptosis rates of celecoxib in the concentrations of 40,60 and 80 μmol/L were significantly higher[-（8.1 ± 0. 9）%, （10. 97± 1.4）% and （19.78± 2.3）% vs. （3.98± 0.6）%] （P〈0.01） and the VEGF, b-FGF and TGF-β mRNA expressions were significantly lower （P〈0.01 ）. Conclusion Celecoxib can effectively inhibit the proliferation and induce apoptosis of AL primary cells, which may be associated with downregulation of the expressions of angiogenesis factors.

关 键 词：塞莱昔布 急性白血病 促血管新生因子 

分 类 号：R733[医药卫生—肿瘤]