Department of Pharmacy, Clinical Medical College, Yangzhou University, Northern Jiangsu People's Hospital, Yangzhou 225001, China.
Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University (The University Key Laboratory of Drug Research), Harbin 150086, China.
Acta Biochim Biophys Sin (Shanghai). 2021 Jul 5;53(7):903-911. doi: 10.1093/abbs/gmab060.
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.
最近的研究表明，7,8-二羟基黄酮（7,8-DHF）抑制了几种肿瘤的发展。然而，它在骨肉瘤（OS）中的作用尚不清楚。本研究旨在探讨 7,8-DHF 对 OS 发展可能有影响的作用和潜在机制。用 7,8-DHF 处理人骨肉瘤细胞系（U2OS 和 143B）；通过甲基噻唑基二苯基四唑溴盐（MTT）测定法和划痕愈合测定法分别评估细胞活力和细胞迁移；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）测定法分别评估细胞死亡和细胞凋亡；使用 2,7-二氯二氢荧光素二乙酸酯探针测量活性氧的产生。通过 Western blot 分析检测 Akt、Bcl-xL/Bcl-2 相关死亡促进剂（Bad）、p38 丝裂原活化蛋白激酶（p38MAPK）、细胞外调节蛋白激酶（ERK）和 c-Jun N-末端激酶（JNK）的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，同时促进 OS 细胞凋亡、抑制迁移并诱导氧化应激。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 抑制 OS 进展，可能通过调节 Akt/Bad 和 MAPK 信号通路。这些发现为 7,8-DHF 的药理作用提供了新的证据，可能改善 OS 患者的药物治疗。
