Abstract

Recent studies suggest that 7,8-dihydroxyflavone (7,8-DHF) inhibits the development of several tumors. However, its role in osteosarcoma (OS) remains unknown. This study was designed to investigate the effects and underlying mechanisms of 7,8-DHF that may influence OS development. Human OS cell lines (U2OS and 143B) were treated with 7,8-DHF; cell viability and cell migration were assessed by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and wound-healing assay, respectively; and cell death and apoptosis were evaluated by LIVE/DEAD staining and terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay, respectively. Reactive oxygen species production was measured using 2,7-dichlorodihydrofluorescein diacetate probe. Akt, Bcl-xL/Bcl-2 asociated death promoter (Bad), p38 mitogen-activated protein kinase (MAPK), extracellular regulated protein kinase (ERK), and c-Jun N-terminal kinase (JNK) expression and their respective phosphorylation levels were detected by western blot analysis. We found that 7,8-DHF reduced cell viability in a dose-dependent manner and also promoted apoptosis, inhibited migration, and induced oxidative stress in OS cells. Moreover, 7,8-DHF inhibited Akt, Bad, and p38MAPK, but activated ERK and JNK signals. In summary, our results suggest that 7,8-DHF inhibits OS progression, possibly by regulating Akt/Bad and MAPK signaling. These findings provide new evidence for the pharmacological effects of 7,8-DHF that may improve drug therapy for OS patients.

中文翻译：

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7,8-二羟基黄酮抑制人骨肉瘤细胞增殖并诱导其凋亡

摘要

最近的研究表明，7,8-二羟基黄酮 (7,8-DHF) 可抑制多种肿瘤的发展。然而，它在骨肉瘤（OS）中的作用仍然未知。本研究旨在调查可能影响 OS 发展的 7,8-DHF 的影响和潜在机制。人 OS 细胞系（U2OS 和 143B）用 7,8-DHF 处理；分别通过甲基噻唑基二苯基溴化四唑 (MTT) 测定和伤口愈合测定评估细胞活力和细胞迁移；细胞死亡和凋亡分别通过 LIVE/DEAD 染色和末端脱氧核苷酸转移酶 (TdT) dUTP 缺口末端标记 (TUNEL) 测定进行评估。使用 2,7-二氯二氢荧光素二乙酸酯探针测量活性氧物质的产生。Akt、Bcl-xL/Bcl-2 相关死亡启动子 (Bad)、p38 丝裂原活化蛋白激酶 (MAPK)、通过蛋白质印迹分析检测细胞外调节蛋白激酶（ERK）和c-Jun N-末端激酶（JNK）表达及其各自的磷酸化水平。我们发现 7,8-DHF 以剂量依赖性方式降低细胞活力，并促进 OS 细胞凋亡、抑制迁移和诱导氧化应激。此外，7,8-DHF 抑制 Akt、Bad 和 p38MAPK，但激活 ERK 和 JNK 信号。总之，我们的结果表明 7,8-DHF 可能通过调节 Akt/Bad 和 MAPK 信号传导来抑制 OS 进展。这些发现为 7,8-DHF 的药理作用提供了新的证据，可以改善 OS 患者的药物治疗。8-DHF 以剂量依赖性方式降低细胞活力，并促进 OS 细胞凋亡、抑制迁移和诱导氧化应激。此外，7,8-DHF 抑制 Akt、Bad 和 p38MAPK，但激活 ERK 和 JNK 信号。总之，我们的结果表明 7,8-DHF 可能通过调节 Akt/Bad 和 MAPK 信号传导来抑制 OS 进展。这些发现为 7,8-DHF 的药理作用提供了新的证据，可以改善 OS 患者的药物治疗。8-DHF 以剂量依赖性方式降低细胞活力，并促进 OS 细胞凋亡、抑制迁移和诱导氧化应激。此外，7,8-DHF 抑制 Akt、Bad 和 p38MAPK，但激活 ERK 和 JNK 信号。总之，我们的结果表明 7,8-DHF 可能通过调节 Akt/Bad 和 MAPK 信号传导来抑制 OS 进展。这些发现为 7,8-DHF 的药理作用提供了新的证据，可以改善 OS 患者的药物治疗。