[糖基化抑制剂2-脱氧-D-葡萄糖使口腔癌细胞对TRAIL诱导的凋亡敏感]

[Glycosylation inhibitor 2-deoxy-D-glucose sensitizes oral cancer cells to TRAIL-induced apoptosis].

作者信息

Xu Jincheng, Huang Yingying, Li Yang, Pu Longjian, Xia Fei, Jiang Chenchen, Liu Hao, Jiang Zhiwen

机构信息

Department of Stomatology, First Affiliated Hospital of Bengbu Medical College, China.

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2013 Apr;33(4):524-7.

PMID:23644112

Abstract

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.

摘要

目的

研究2-脱氧-D-葡萄糖（2-DG）增强口腔癌细胞对肿瘤坏死因子相关凋亡诱导配体（TRAIL）诱导凋亡敏感性的作用。

方法

将口腔癌细胞系KB在不同浓度（0、0.625、1.25、2.5、5和10 mmol/L）的2-DG存在下孵育，同时加入或不加入TRAIL（200 ng/ml）。使用MTT法测定细胞活力，采用碘化丙啶（PI）染色的流式细胞术检测细胞凋亡。用5 mmol/L 2-DG处理KB细胞，加入或不加入TRAIL，分别处理0、6、16或24小时，然后用蛋白质印迹法检测死亡受体5（DR5）和半胱天冬酶-3的蛋白表达。

结果

用5 mmol/L 2-DG处理细胞24、48和72小时后，细胞活力分别为25.25%、69.06%和59.19%。与单独使用TRAIL（45.3%）或2-DG（15.9%）相比，5 mmol/L 2-DG与TRAIL联合处理24小时显著提高了细胞凋亡率（72.5%）。2-DG处理显著上调了DR5和半胱天冬酶-3的表达，并增强了TRAIL对细胞集落形成的抑制作用。