Polyphyllin I 通过下调 Wnt/β-catenin 通路,增强肿瘤坏死因子相关凋亡诱导配体对人骨肉瘤细胞生长的抑制作用。

Chang Junli, Zhao Fulai, Sun Xingyuan, M A Xiaoping, Zhao Peng, Zhou Chujie, Shi Binhao, G U Wenchao, Wang Yongjun, Yang Yanping
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摘要

目的研究多粘菌素 I(PPI)与肿瘤坏死因子相关凋亡诱导配体(TRAIL)通过下调 Wnt/β-catenin 信号通路对骨肉瘤细胞生长的协同作用:方法:使用细胞计数试剂盒-8 和流式细胞术检测细胞活力、凋亡和细胞周期分布。倒置相差显微镜观察癌细胞的形态。迁移和侵袭能力由 xCELLigence 实时细胞分析 DP 系统和透孔试验检测。用 Western 印迹法测定了多(腺苷二磷酸核糖)聚合酶、C-Myc、细胞周期蛋白 B1、细胞周期蛋白依赖性激酶 1、N-钙粘蛋白、波形蛋白、活性-β-catenin、β-catenin、p-糖原合成酶激酶 3β (GSK-3β)和 GSK-3β 的表达:结果:PPI对TRAIL诱导的MG-63和U-2 OS骨肉瘤细胞活力、迁移和侵袭的降低以及细胞凋亡和细胞周期停滞的增加具有敏化作用。PPI与TRAIL在抑制骨肉瘤细胞生长方面的协同作用至少部分是通过Wnt/β-catenin信号通路的失活实现的:结论:PPI与TRAIL的联合应用可能是治疗骨肉瘤的一种新策略。
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Polyphyllin I enhances tumor necrosis factor-related apoptosis-inducing ligand-induced inhibition of human osteosarcoma cell growth downregulating the Wnt/β-catenin pathway.

Objective: To investigate the synergistic effects of polyphyllin I (PPI) combined with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on the growth of osteosarcoma cells through downregulating the Wnt/β-catenin signaling pathway.

Methods: Cell viability, apoptosis and cell cycle distribution were examined using cell counting kit-8 and flow cytometry assays. The morphology of cancer cells was observed with inverted phase contrast microscope. The migration and invasion abilities were examined by xCELLigence real time cell analysis DP system and transwell assays. The expressions of poly (adenosine diphosphate-ribose) polymerase, C-Myc, Cyclin B1, cyclin-dependent kinases 1, N-cadherin, Vimentin, Active-β-catenin, β-catenin, p-glycogen synthase kinase 3β (GSK-3β) and GSK-3β were determined by Western blotting assay.

Results: PPI sensitized TRAIL-induced decrease of viability, migration and invasion, as well as increase of apoptosis and cell cycle arrest of MG-63 and U-2 OS osteosarcoma cells. The synergistic effect of PPI with TRAIL in inhibiting the growth of osteosarcoma cells was at least partially realized through the inactivation of Wnt/β-catenin signaling pathway.

Conclusion: The combination of PPI and TRAIL is potentially a novel treatment strategy of osteosarcoma.

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