| 3 | 黄酮类化合物紫花牡荆素通过内质网应激上调死亡受体5促进TRAIL诱导的结肠癌细胞凋亡(英文)显示文摘Objective:The aim of this study was to explore the mechanisms by which the flavonoid casticin enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in colon cancer cells. Methods:Human colon cancer HT-29 cells were treated with TRAIL or casticin. Cytotoxicity was examined by MTT assay, and apoptosis determined by morphological observation and flow cytometric analysis. Death receptor 5 (DR5), DR4, and endoplasmic reticulum (ER) stress response markers, including glucose regulating protein 78 (GRP78), activating transcription factor 4 (ATF4) and CHOP (CCAAT/enhancer binding protein homologous protein), were examined with western blot. Small interfering RNA (siRNA) transfection was employed to knock down CHOP. Results:HT-29 cells were resistance to TRAIL-induced apoptosis, but casticin, at subtoxic concentrations, potentiated HT-29 cells to TRAIL-induced apoptosis. Casticin up-regulated the expression of DR5 time-and dose-dependent manners, but had no effect on the expression of DR4. Also, casticin increased the levels of ER stress response markers (GRP78, ATF4 and CHOP) in a similar way to DR5. Knockdown of CHOP by specific siRNA, or salubrinal, an ER stress inhibitor, abolished the up-regulation of DR5 and enhancement of TRAIL-induced apoptosis by casticin. Conclusion:Casticin enhances TRAIL-induced apoptosis of colon cancer cells by ER stress-mediated up-regulation of DR5. | Sanyuan Tang Guangjin Yuan Zhengyang Yu Leilan Yin Hao Jiang | 2013 | The Chinese-German Journal of Clinical Oncology2013，12，6： | 0 |
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