Ginsenoside Rg5 Inhibits Human Osteosarcoma Cell Proliferation and Induces Cell Apoptosis through PI3K/Akt/mTORC1-Related LC3 Autophagy Pathway

被引:45
作者
Liu, Ming-Yang [1 ,2 ]
Liu, Fei [3 ]
Li, Yan-Jiao [4 ]
Yin, Jia-Ning [5 ]
Gao, Yan-Li [5 ]
Wang, Xin-Yue [6 ]
Yang, Chen [2 ]
Liu, Jian-Guo [2 ]
Li, Hai-Jun [1 ]
机构
[1] Jilin Univ, Inst Translat Med, Dept Immun, Hosp 1, Changchun, Peoples R China
[2] Jilin Univ, Dept Orthopaed, Hosp 1, Changchun, Peoples R China
[3] Jilin Univ, Dept Obstet, Hosp 1, Changchun, Peoples R China
[4] Jilin Univ, Dept Pharm, Hosp 1, Changchun, Peoples R China
[5] Jilin Univ, Dept Pediat, Hosp 1, Changchun, Peoples R China
[6] Jilin Univ, Coll Basic Med, Dept Sci Res, Changchun, Peoples R China
基金
中国国家自然科学基金;
关键词
Chemical activation - Cell death;
D O I
10.1155/2021/5040326
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
The function and mechanism underlying the suppression of human osteosarcoma cells by ginsenoside-Rg5 (Rg5) was investigated in the present study. MG-63, HOS, and U2OS cell proliferation was determined by MTT assay after Rg5 treatment for 24 h. Rg5 inhibited human osteosarcoma cell proliferation effectively in a dose-dependent manner. The range of effective inhibitory concentrations was 160-1280 nM. Annexin V-FITC and PI double-staining assay revealed that Rg5 induced human osteosarcoma cell apoptosis. Western blotting, qRT-PCR, and FACS experiments revealed that Rg5 inhibited human osteosarcoma cells via caspase-3 activity which was related to the LC3-mediated autophagy pathway. Rg5 decreased the phosphorylation of PI3K, Akt, and mTORC1 activation. In contrast, LC3-mediated autophagy and caspase-3 activity increased significantly. A PI3K/AKT stimulator, IGF-1, reversed Rg5-induced cell autophagy and apoptosis in MG-63 cells. Collectively, the current study demonstrated that Rg5 induced human osteosarcoma cell apoptosis through the LC3-mediated autophagy pathway. Under physiological conditions, activation of PI3K/AKT/mTORC1 inhibits LC3 activity and caspase-3-related cell apoptosis. However, Rg5 activated LC3 activity by inhibiting the activation of PI3K/AKT/mTORC1. The present study indicated that Rg5 could be a promising candidate as a chemotherapeutic agent against human osteosarcoma.
引用
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页数:12
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