Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea; Institute of Animal Molecular Biotechnology, Korea University, Seoul, 02841, Republic of Korea.
Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea.
J Ethnopharmacol. 2019 May 23;236:393-400. doi: 10.1016/j.jep.2019.03.031. Epub 2019 Mar 13.
Korean Red ginseng extract (RG) is one of the most widely used traditional health functional food in Asia, which invigorates immunity and vital energy. RG have been suggested to inhibit proliferation, invasion, and inflammation in several cancer cell lines. Correspondingly, clinical studies have raised the possibility that RG could augment therapeutic efficacy in cancer patients. However, little is known about the anti-cancer effects of RG in glioblastoma (GBM), the most common and aggressive brain tumor for which effective therapeutic regimens need to be developed.
Here, we assessed the in vivo and in vitro anti-cancer properties of RG in a patient-derived xenograft mouse model and GBM stem cell (GSC) line.
We evaluated the anti-cancer effects of RG in patient-derived GBM xenograft mice with and without combined concurrent chemo- and radiation therapy (CCRT). Furthermore, we verified the in vitro effects of RG on the proliferation, cell death, and stem cell-like self-renewal capacity of cancer cells. Finally, we investigated the signaling pathway affected by RG, via which its anti-cancer effects were mediated.
When combined with CCRT, RG impeded GBM progression by reducing cancer cell proliferation and ionized calcium-binding adapter molecule 1 (IBA1)-positive immune cell recruitment. The anti-cancer effects of RG were mediated by Rg3 and Rh2 ginsenosides. Rg3 promoted cell death while Rh2 did not. Furthermore, both Rg3 and Rh2 reduced cell viability and self-renewal capacity of GSCs by inhibiting Wnt/β-catenin signaling.
Therefore, our observations imply that RG could be applied to the GBM patients in parallel with CCRT to enhance therapeutic efficacy.
红参提取物(RG)是亚洲最广泛使用的传统健康功能性食品之一,具有增强免疫力和活力的作用。RG 已被证明可抑制几种癌细胞系的增殖、侵袭和炎症。相应地,临床研究提出了 RG 可能增强癌症患者治疗效果的可能性。然而,对于 RG 在胶质母细胞瘤(GBM)中的抗癌作用知之甚少,GBM 是最常见和侵袭性的脑肿瘤,需要开发有效的治疗方案。
本研究评估了 RG 在患者来源的异种移植小鼠模型和 GBM 干细胞(GSC)系中的体内和体外抗癌特性。
我们评估了 RG 在伴有和不伴有联合化疗和放疗(CCRT)的患者来源的 GBM 异种移植小鼠中的抗癌作用。此外,我们验证了 RG 对癌细胞增殖、细胞死亡和干细胞样自我更新能力的体外影响。最后,我们研究了 RG 影响的信号通路,通过该通路介导其抗癌作用。
当与 CCRT 联合使用时,RG 通过减少癌细胞增殖和离子钙结合接头分子 1(IBA1)阳性免疫细胞募集来阻碍 GBM 的进展。RG 的抗癌作用是由 Rg3 和 Rh2 人参皂苷介导的。Rg3 促进细胞死亡,而 Rh2 则没有。此外,Rg3 和 Rh2 通过抑制 Wnt/β-catenin 信号通路降低 GSCs 的细胞活力和自我更新能力。
因此,我们的观察结果表明,RG 可以与 CCRT 一起应用于 GBM 患者,以增强治疗效果。