Objective To investigate the effect of 2-deoxy-D-glucose (2-DG) in enhancing the sensitivity of oral cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Methods The oral cancer cell line KB was incubated in the presence of different concentrations (0, 0.625,1.25, 2.5, 5, and 10 mmol/L) of 2-DG with or without TRAIL (200 ng/ml). The cell viability was measured using MTT assay and cell apoptosis was detected using flow cytometry with propidium iodide (PI) staining. KB cells treated with 5 mmol/L 2-DG with or without TRAIL for 0, 6,16, or 24 h were examined with Western blotting for protein expressions of death receptor 5 (DR5) and caspase-3. Results Treatment of the cells with 5 mmol/L 2-DG for 24, 48 and 72 h resulted in a cell viability of 25.25%, 69.06%, and 59.19%, respectively. Combined treatment with 5 mmol/L 2-DG with TRAIL for 24 significantly enhanced the cell apoptotic rate (72.5%) as compared to the rate induced by TRAIL alone (45.3%) and by 2-DG (15.9%) alone. 2-DG treatment markedly up-regulated DR5 and caspase-3 expression and enhanced the inhibitory effect of TRAIL on cell colony formation. Conclusion 2-DG sensitizes oral cancer cells to TRAIL-induced apoptosis by up-regulating DR5 and caspase-3 expressions.%目的 探讨糖基化抑制剂2-脱氧葡萄糖(2-DG)对肿瘤坏死因子相关凋亡诱导配体(TRAIL)诱导肿瘤细胞凋亡作用的影响.方法 MTT法检测不同浓度(0、0.625、1.25、2.5、5、10 mmol/L)2-DG及不同浓度2-DG与TRAIL(200 ng/ml)合用对口腔癌细胞KB的增殖抑制作用.集落克隆法检测2-DG及TRAIL对口腔癌细胞KB的增殖抑制作用.溴化丙啶(PI)单染法检测2-DG(5 mmol/L)对TRAIL诱导口腔癌细胞KB凋亡的影响；Western blot检测2-DG(5 mmol/L)处理口腔癌细胞KB不同时间(0、6、16、24h),DR5的表达以及联合TRAIL处理后Caspase-3的表达.结果 5mmol/L 2-DG作用于口腔癌细胞KB24、48、72 h细胞存活率分别为75.25％、69.06％、59.19％,但24 h细胞凋亡率仅为15.9％.5mmol/L 2-DG与TRAIL联合作用于口腔癌细胞KB 24h的凋亡率为72.5％,高于TRAIL本身诱导凋亡率45.3％,并且2-DG可增强TRAIL抑制口腔癌细胞KB的集落克隆形成的作用.2-DG上调DR5的表达并且增强Caspase-3的激活.结论 2-DG能增强TRAIL诱导口腔癌细胞的凋亡,其机制可能是上调DR5的表达及增强Caspase-3的激活.
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