Li Yan, Yang Tao, Li Jing, Hao Hong-Ling, Wang Su-Yun, Yang Jie, Luo Jian-Min
Department of Hematology, The Second Hospital, Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.
Department of Urinary Surgery, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China.
Mol Med Rep. 2016 Sep;14(3):2222-30. doi: 10.3892/mmr.2016.5475. Epub 2016 Jul 7.
Ginsenoside Rg3 (Rg3) is one of the primary constituents isolated from ginseng, and has been found to exhibit cytotoxic effects against cancer cells. The present study aimed to investigate the effects of Rg3 on human multiple myeloma cell proliferation and apoptosis, and to examine its underlying molecular mechanisms. Cell viability was detected using a Cell Counting kit‑8 assay, and cell cycle arrest and cell apoptosis were analyzed using flow cytometry. In addition, the expression levels of cell cycle‑associated markers and apoptosis‑associated proteins, and the release of cytochrome C were determined using western blot analysis. The effects of Rg3 on the insulin‑like growth factor (IGF)-1/AKT/mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase signaling pathways were also investigated using western blot analysis. The results showed that Rg3 inhibited cell viability in U266, RPMI8226 and SKO‑007 cells in a time‑ and dose‑dependent manner, and caused cell cycle arrest in the G1 phase by regulating the cyclin‑dependent kinase pathway. Furthermore, Rg3 induced multiple myeloma cell apoptosis, and was involved in B cell lymphoma-2 (Bcl2)/Bcl2-associated X protein imbalance, caspase activation and the release of cytochrome C from the mitochondria into the cytoplasm. Mechanistically, it was found that the inhibitory effects of Rg3 on multiple myeloma cell proliferation were essential for secretion of IGF‑1 and inactivation of the Akt/mTOR pathway. Collectively, these findings demonstrated that Rg3 effectively inhibited cell proliferation and induced apoptosis of multiple myeloma cells. These data broaden the clinical investigation of Rg3 in the treatment of multiple myeloma, associated with the inactivation of IGF-1/AKT/mTOR signaling.
人参皂苷Rg3（Rg3）是从人参中分离出的主要成分之一，已被发现对癌细胞具有细胞毒性作用。本研究旨在探讨Rg3对人多发性骨髓瘤细胞增殖和凋亡的影响，并研究其潜在的分子机制。使用细胞计数试剂盒-8检测细胞活力，采用流式细胞术分析细胞周期阻滞和细胞凋亡。此外，通过蛋白质印迹分析确定细胞周期相关标志物和凋亡相关蛋白的表达水平以及细胞色素C的释放。还使用蛋白质印迹分析研究了Rg3对胰岛素样生长因子（IGF）-1/蛋白激酶B（AKT）/雷帕霉素哺乳动物靶蛋白（mTOR）和丝裂原活化蛋白激酶信号通路的影响。结果表明，Rg3以时间和剂量依赖性方式抑制U266、RPMI8226和SKO-007细胞的活力，并通过调节细胞周期蛋白依赖性激酶途径使细胞周期阻滞在G1期。此外，Rg3诱导多发性骨髓瘤细胞凋亡，并参与B细胞淋巴瘤-2（Bcl2）/Bcl2相关X蛋白失衡、半胱天冬酶激活以及细胞色素C从线粒体释放到细胞质中。机制上，发现Rg3对多发性骨髓瘤细胞增殖的抑制作用对于IGF-1的分泌和Akt/mTOR途径的失活至关重要。总的来说，这些发现表明Rg3有效抑制多发性骨髓瘤细胞的增殖并诱导其凋亡。这些数据拓宽了Rg3在治疗多发性骨髓瘤方面的临床研究，这与IGF-1/AKT/mTOR信号失活有关。
