中文摘要：

目的探讨糖基化抑制剂2-脱氧葡萄糖（2deoxyDglucose, 2DG）对肿瘤坏死因子相关凋亡诱导配体（tumors necrosis factorrelated apotosisinducing ligand, TRAIL）诱导肿瘤细胞凋亡作用的影响，以期为鼻咽癌的治疗提供新的靶点。方法MTT法检测不同浓度（0、0625、125、25、5、10 mmol·L-1）2DG以及不同浓度2-DG与TRAIL（200 μg·L-1）合用对鼻咽癌细胞CNE2的增殖抑制作用。溴化丙啶（propidium iodide, PI）单染检测2DG（5 mmol·L-1）对TRAIL诱导鼻咽癌细胞CNE2凋亡的影响；Western blot检测2DG（5 mmol·L-1）处理鼻咽癌细胞CNE2不同时间（0、6、16、24 h）葡萄糖调节蛋白（glucoseregulated protein 78, GRP78）以及联合TRAIL处理后Caspase3的表达；实验中检测了2-DG及TRAIL合用对集落克隆形成的影响。结果5 mmol·L-1 2-DG作用于鼻咽癌细胞CNE-2 24、48、72 h细胞存活率分别为7696%、7083%、6939%，而诱导CNE-2 24 h细胞凋亡率仅为77%。5 mmol·L-1 2-DG与TRAIL联合作用于鼻咽癌细胞CNE-2 24 h的凋亡率为78.9%，高于TRAIL单用诱导凋亡率38.2%，并且2-DG可增强TRAIL抑制鼻咽癌细胞CNE2的集落克隆形成的作用。2-DG能上调GRP78的活性并且增强Caspase-3的激活。结论2DG能增强TRAIL诱导鼻咽癌细胞的凋亡，其机制可能通过引起过度的内质网应激反应以及增强Caspase-3的激活。

英文摘要：

Aim To determine whether 2-DG （2-deoxy-D-glucose） can synergize with tumors necrosis fac- tor-related apotosis-inducing ligand （TRAIL） which is used in nasopharyngeal carcinoma treatment and wish to find new targets for human nasopharyngeal carcinoma chemotherapy. Methods Nasopharyngeal carcinoma cells CNE-2 were incubated with varying concentrations of 2-DG （0, 0.625, 1.25, 2.5, 5, 10 mmol · L-1） with or without TRAIL （200 μg · L- l ）. Cell viability was measured by the MTF （3-（4, 5-dimethylthiazol-2- yl ） -2-5 diphenyltetrazolium bromide ） assay. Then propidium iodide （PI） staining was used to measure ap- optotic cells in Flow Cytometry （FCM）. CNE-2 cells were treated with 2-DG （5 mmol· L-1） （with or without TRAIL） for different time points （0, 6, 16, 24 h）. Western blot was used to measure the protein expression of glucose-regulated protein 78 （ GRP-78 ） and Caspase-3. Results Combining 2-DG with TRAIL resulted in enhanced cell death compared with the individual use of each agent, 2-DG induced apoptosis cells hardly reached 10% and 2-DG markedly up-regulated GRP-78 and Caspase-3 expression. With the combination of 2-DG and TRAIL, the apoptotic rate of CNE-2 cells reached 78.9%. Conclusion These results indicate that 2-DG sensitizes nasopharyngeal carcinoma cells to TRAIL induced apoptosis by up-regulation of GRP-78 and Caspase-3.