Department of Orthopedics, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
Department of Orthopedics, Changde Hospital, Xiangya School of Medicine, Central South University, Changde, Hunan, China.
J Pharm Pharmacol. 2023 Nov 23;75(11):1405-1417. doi: 10.1093/jpp/rgad070.
The most common cause of osteosarcoma (OS) death is lung metastasis. Currently, doxorubicin is the primary chemotherapy drug used to treat OS, however, it is not effective in inhibiting metastasis, and it has obvious cardiotoxicity. The anticancer activity of ginsenoside Rg3 has been demonstrated in a variety of malignant tumours. The aim of this study was to determine the potential role of ginsenoside Rg3 and doxorubicin in OS and the possible mechanism.
The potential synergistic effects of ginsenoside Rg3 and doxorubicin on human osteosarcoma cells 143B and U2OS, human umbilical vein endothelial cells, and mice receiving 143B xenografts and lung metastases were investigated.
Our study demonstrated that the combination of ginsenoside Rg3 and doxorubicin significantly inhibited cell proliferation, metastasis and angiogenesis in vitro. Mechanically, the anti-tumour activity of ginsenoside Rg3 and doxorubicin by modulating mTOR/HIF-1α/VEGF and EMT signalling pathways. Furthermore, ginsenoside Rg3 combined with doxorubicin inhibits tumour growth and lung metastasis in 143B-derived murine osteosarcoma models. More importantly, ginsenoside Rg3 can effectively ameliorate doxorubicin-induced weight loss and cardiotoxicity in mice.
Consequently, we concluded that the combination of ginsenoside Rg3 and doxorubicin displayed an evidently synergistic effect, which has the potential to be used as an effective and safe therapeutic approach for OS treatment.
骨肉瘤（OS）死亡的最常见原因是肺转移。目前，阿霉素是治疗骨肉瘤的主要化疗药物，但它不能有效抑制转移，且具有明显的心脏毒性。人参皂苷 Rg3 在多种恶性肿瘤中表现出抗癌活性。本研究旨在确定人参皂苷 Rg3 和阿霉素在骨肉瘤中的潜在作用及其可能的机制。
研究了人参皂苷 Rg3 和阿霉素对人骨肉瘤细胞 143B 和 U2OS、人脐静脉内皮细胞以及接受 143B 异种移植和肺转移的小鼠的潜在协同作用。
我们的研究表明，人参皂苷 Rg3 和阿霉素的联合显著抑制了体外细胞增殖、转移和血管生成。在机制上，通过调节 mTOR/HIF-1α/VEGF 和 EMT 信号通路，人参皂苷 Rg3 和阿霉素发挥抗肿瘤活性。此外，人参皂苷 Rg3 联合阿霉素抑制了 143B 衍生的骨肉瘤小鼠模型中的肿瘤生长和肺转移。更重要的是，人参皂苷 Rg3 可有效改善小鼠阿霉素引起的体重减轻和心脏毒性。
因此，我们得出结论，人参皂苷 Rg3 和阿霉素联合具有明显的协同作用，有可能成为治疗骨肉瘤的有效、安全的治疗方法。
