College of Pharmacy, Sookmyung Womens University, Seoul 140-742, Republic of Korea.
Biomol Ther (Seoul). 2012 Jan;20(1):62-7. doi: 10.4062/biomolther.2012.20.1.062.
TNF-related apoptosis-inducing ligand (TRAIL) is a promising agent for management of cancer because of its selective cytotoxicity to cancer cells. However, some cancer cells have resistance to TRAIL. Accordingly, novel treatment strategies are required to overcome TRAIL resistance. Here, we examined the synergistic apoptotic effect of apigenin in combination with TRAIL in Huh-7 cells. We found that combined treatment of TRAIL and apigenin markedly inhibited Huh-7 cell growth compared to either agent alone by inducing apoptosis. Combined treatment with apigenin and TRAIL induced chromatin condensation and the cleavage of poly (ADP-ribose) polymerase (PARP). In addition, enhanced apoptosis by TRAIL/apigenin combination was quantified by annexin V/PI flow cytometry analysis. Western blot analysis suggested that apigenin sensitizes cells to TRAIL-induced apoptosis by activating both intrinsic and extrinsic apoptotic pathway-related caspases. The augmented apoptotic effect by TRAIL/apigenin combination was accompanied by triggering mitochondria-dependent signaling pathway, as indicated by Bax/Bcl-2 ratio up-regulation. Our results demonstrate that combination of TRAIL and apigenin facilitates apoptosis in Huh-7 cells.
肿瘤坏死因子相关凋亡诱导配体（TRAIL）因其对癌细胞的选择性细胞毒性而成为癌症治疗的一种有前途的药物。然而，一些癌细胞对 TRAIL 具有抗性。因此，需要新的治疗策略来克服 TRAIL 耐药性。在这里，我们研究了白杨素与 TRAIL 联合应用对 Huh-7 细胞的协同凋亡作用。我们发现，与单独使用任何一种药物相比，TRAIL 和白杨素联合治疗可通过诱导细胞凋亡显著抑制 Huh-7 细胞的生长。联合使用白杨素和 TRAIL 诱导染色质浓缩和聚（ADP-核糖）聚合酶（PARP）的裂解。此外，通过 Annexin V/PI 流式细胞术分析定量了 TRAIL/白杨素联合治疗的增强凋亡作用。Western blot 分析表明，白杨素通过激活内在和外在凋亡途径相关半胱天冬酶使细胞对 TRAIL 诱导的凋亡敏感。TRAIL/白杨素联合治疗的增强凋亡作用伴随着触发线粒体依赖性信号通路，如 Bax/Bcl-2 比值上调所表明的那样。我们的结果表明，TRAIL 和白杨素的联合促进了 Huh-7 细胞的凋亡。
