蛋白激酶B
PI3K/AKT/mTOR通路
碘化丙啶
膜联蛋白
细胞凋亡
癌症研究
活力测定
细胞生长
化学
表皮生长因子受体
骨肉瘤
信号转导
表皮生长因子
细胞生物学
生物
程序性细胞死亡
受体
生物化学
作者
Richard Zhu,Jiajia Zhang,Xiaobin Yao,Zhang-Jiao Wang,Zhaohui Du,Qingxia Xu
标识
DOI:10.1177/09731296231215938
摘要
Background: Shikonin, a purified naphthoquinone separated from a Traditional Chinese medicinal herb Lithospermum erythrorhixon, which exhibits anticancer properties. Objective: To clarify the molecular mechanisms of therapeutic effects of shikonin against osteosarcoma. Methods: Cell Counting Kit-8 (CCK-8) assay was employed to evaluate cell viability. Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) double-staining was conducted to evaluate the apoptotic ratio of the MG-63 cells. The effects of shikonin on the invasiveness of osteosarcoma cells were implemented by a transwell cell migration assay. In the meantime, a western blot assay was employed to detect alterations in the relevant mechanism proteins within osteosarcoma cells. Molecular docking analysis was conducted to anticipate the binding interaction between shikonin and EGFR/protein kinase B (AKT)/mTOR. Results: We observed that shikonin suppressed proliferation and induced apoptosis in the MG-63 cells in a dose-dependent manner. Pursuing these findings, the potential molecular mechanisms were detected. Shikonin intervention blocked epidermal growth factor receptor (EGFR) phosphorylation and decreased epidermal growth factor (EGF)-induced activation of downstream signaling molecules, such as AKT and mammalian target of rapamycin (mTOR) in the MG-63 cells. However, the additional recombinant human epidermal growth factor (rHuEGF) could stimulate the activation of EGFR/AKT/mTOR signaling and reverse cell apoptosis caused by shikonin. Molecular docking analysis showed that shikonin presented the highest bonding ability with EGFR, AKT, and mTOR. Conclusion: Our results show that shikonin inhibits human osteosarcoma development via inactivating EGFR/AKT/mTOR signaling. It demonstrates that shikonin may act as a potential therapeutic agent in osteosarcoma treatment.
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