title: Inhibition of multiple myeloma cell proliferation by ginsenoside Rg3 via reduction in the secretion of IGF-1.
abstract: 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.
authors.affiliation: Department of Hematology, The Second Hospital, Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Urinary Surgery, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Hematology, Hebei Province Chinese Medicine Hospital, Shijiazhuang, Hebei 050011, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Hematology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China.
authors.forename: Hong-Ling
authors.initials: HL
authors.lastname: Hao
authors.affiliation: Department of Hematology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China.
authors.forename: Su-Yun
authors.initials: SY
authors.lastname: Wang
authors.affiliation: Department of Hematology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Hematology, The Second Hospital, Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Luo
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009101:Multiple Myeloma / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D036145:Ginsenosides; C097367:ginsenoside Rg3; D007334:Insulin-Like Growth Factor I; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases