PMID- 27430248 OWN - NLM STAT- MEDLINE DCOM- 20170406 LR - 20220316 IS - 1791-3004 (Electronic) IS - 1791-2997 (Linking) VI - 14 IP - 3 DP - 2016 Sep TI - Inhibition of multiple myeloma cell proliferation by ginsenoside Rg3 via reduction in the secretion of IGF-1. PG - 2222-30 LID - 10.3892/mmr.2016.5475 [doi] AB - 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. FAU - Li, Yan AU - Li Y AD - Department of Hematology, The Second Hospital, Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China. FAU - Yang, Tao AU - Yang T AD - Department of Urinary Surgery, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China. FAU - Li, Jing AU - Li J AD - Department of Hematology, Hebei Province Chinese Medicine Hospital, Shijiazhuang, Hebei 050011, P.R. China. FAU - Hao, Hong-Ling AU - Hao HL AD - Department of Hematology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China. FAU - Wang, Su-Yun AU - Wang SY AD - Department of Hematology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China. FAU - Yang, Jie AU - Yang J AD - Department of Hematology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China. FAU - Luo, Jian-Min AU - Luo JM AD - Department of Hematology, The Second Hospital, Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China. LA - eng PT - Journal Article DEP - 20160707 PL - Greece TA - Mol Med Rep JT - Molecular medicine reports JID - 101475259 RN - 0 (Ginsenosides) RN - 227D367Y57 (ginsenoside Rg3) RN - 67763-96-6 (Insulin-Like Growth Factor I) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Apoptosis/drug effects MH - Cell Cycle/drug effects MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Cell Survival/drug effects MH - Ginsenosides/*pharmacology MH - Humans MH - Insulin-Like Growth Factor I/*metabolism MH - Mitochondria/drug effects/metabolism MH - Mitogen-Activated Protein Kinases/metabolism MH - Multiple Myeloma/*metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - Signal Transduction/drug effects MH - TOR Serine-Threonine Kinases/metabolism EDAT- 2016/07/20 06:00 MHDA- 2017/04/07 06:00 CRDT- 2016/07/20 06:00 PHST- 2015/07/21 00:00 [received] PHST- 2016/05/31 00:00 [accepted] PHST- 2016/07/20 06:00 [entrez] PHST- 2016/07/20 06:00 [pubmed] PHST- 2017/04/07 06:00 [medline] AID - 10.3892/mmr.2016.5475 [doi] PST - ppublish SO - Mol Med Rep. 2016 Sep;14(3):2222-30. doi: 10.3892/mmr.2016.5475. Epub 2016 Jul 7.