中文摘要：

目的 ：研究硼替佐米（bortezomib,BTZ）联合寡霉素（oligomycin,OM）对Burkitt淋巴瘤Raji细胞增殖及凋亡的影响,并探讨可能的作用机制。方法：采用不同浓度的BTZ（0、5、10、15、20、25和30 nmol/L）单药或联合OM（0.05μg/m L）作用于Raji细胞,CCK-8法检测对细胞增殖抑制率的影响;实时荧光定量PCR法和蛋白质印迹法检测原癌基因C-myc、缺氧诱导因子1α（hypoxia-inducible factor-1α,HIF-1α）及其靶基因血管内皮生长因子（vascular endothelial growth factor,VEGF）和葡萄糖转运体1（glucose transporter 1,GLUT1）m RNA及蛋白的表达,以及代谢途径中关键酶己糖激酶Ⅱ（hexokinaseⅡ,HKⅡ）、乳酸脱氢酶（lactic dehydrogenase,LDHA）和琥珀酸脱氢酶（succinate dehydrogenase,SDHA）m RNA及蛋白表达水平的变化;葡萄糖检测试剂盒[己糖激酶（hexokinase,HK）法]和乳酸检测试剂盒分别检测Raji细胞培养液中葡萄糖和乳酸浓度的改变;FCM法检测细胞周期分布及细胞凋亡的改变。结果 ：不同浓度的BTZ单药作用于Raji细胞后,可明显抑制Raji细胞的增殖且呈剂量依赖性（P值均〈0.01）。BTZ（5、10、15和20 nmol/L）联合OM对Raji细胞的增殖抑制率显著高于BTZ单药组（P值均〈0.01）。BTZ单药作用于Raji细胞后,可不同程度抑制细胞中C-myc、HIF-1α、VEGF、GLUT1、HKⅡ、LDHA及SDHA m RNA及蛋白的表达;联合OM处理Raji细胞后,代谢相关基因m RNA及蛋白的表达水平进一步下调（P值均〈0.05）。联合用药组抑制葡萄糖消耗及糖酵解代谢产物乳酸生成的能力明显高于BTZ单药组（P值均〈0.05）。BTZ单药组能明显促进Raji细胞的凋亡且呈剂量依赖性,BTZ浓度为25 nmol/L时,Raji细胞主要被阻滞于G2/M期;而联合用药组能进一步提高细胞的凋亡率,BTZ浓度为5和15 nmol/L时,Raji细胞主要被阻滞于G0/G1期。结论 ：BTZ可抑制Raji细胞的糖酵解通路,联合OM可协同增强这一抑制作用,这种?

英文摘要：

Objective： To investigate the effect of bortezomib（BTZ） in combination with aerobic oxidation inhibitor oligomycin（OM） on proliferation and apoptosis of Burkitt lymphoma cell line Raji, and to explore its possible molecular mechanism.Methods： Raji cells were treated with different concentrations of BTZ（0, 5, 10, 15, 20, 25 and 30 nmol/L） alone or in combination with OM（0.05 μg/m L）. Cell proliferation was detected by CCK-8 method. The m RNA and protein expression levels of oncogene C-myc, hypoxiainducible factor-1α（HIF-1α） and its target genes vascular endothelial growth factor（VEGF） and glucose transporter 1（GLUT1）, and key enzymes and proteins related to glycolysis pathway including hexokinase Ⅱ（HKⅡ）, lactic dehydrogenase（LDHA） and succinate dehydrogenase（SDHA） were detected by real-time fluorescent quantitative PCR and Western blotting, respectively. Glucose consumption and lactic acid generation were examined by Glucose（hexokinase, HK） Assay Kit and Lactate Assay Kit, respectively. Apoptosis and cell cycle distribution were analyzed by FCM.Results： The result of CCK-8 method showed that treatment with different concentrations of BTZ could inhibit the proliferation of Raji cells in a dose-dependent manner（all P 0.01）, the inhibition effect was significantly enhanced at lower initial concentrations of BTZ（5, 10, 15 and 20 nmol/L） in combination with OM（all P 0.01）. The expression levels of C-myc, HIF-1α, VEGF, GLUT1, HKⅡ, LDHA and SDHA m RNAs and proteins were suppressed by BTZ, and the expression levels were further down-regulated due to treatment with BTZ in combination with OM（all P 0.05）. The inhibition of glucose consumption and lactic acid generation induced by BTZ in combination with OM was significantly enhanced as compared with those induced by BTZ alone（both P 0.05）. The result of FCM showed that BTZ could induce apoptosis of Raji cells in a dose-dependent manner, and the cell cycle was arrested in G2/M phase under a relat