title: Silybin suppresses cell proliferation and induces apoptosis of multiple myeloma cells via the PI3K/Akt/mTOR signaling pathway.
abstract: Silybin is a biologically active component extracted from the seeds of Silybum marianum, which has been shown to have inhibitory effects on prostate, skin, bladder, lung and colon cancer cells, in addition to its efficacy in the treatment of liver diseases, including hepatitis and cirrhosis. The aim of the present study was to investigate whether silybin suppresses the proliferation and induces apoptosis of multiple myeloma (MM) cells and to elucidate its molecular targets. The proliferative and apoptotic rates of the U266 MM cell line were assessed using MTT and flow‑cytometric assays, respectively. Western blot analysis was used to assess the protein levels of phosphoinositide‑3 kinase (PI3K), phosphorylated (p)‑Akt and p‑mammalian target of rapamycin (mTOR) in U266 cells. In addition, PI3K inhibitor LY294002 or activator insulin‑like growth factor 1 were used to investigate the involvement of the PI3K/Akt‑mTOR signaling pathway in the effect of silybin on U266 cells. The results revealed that silybin restrained the proliferation and enhanced the apoptosis of U266 cells. Furthermore, silybin inhibited the protein expression of PI3K, p‑Akt and p‑mTOR in U266 cells. Of note, inhibition of PI3K facilitated silybin‑mediated reduction of mTOR activation, cell proliferation and induction of apoptosis in U266 cells, while activation of PI3K attenuated the effects of silybin. In conclusion, silybin suppressed cell proliferation and promoted apoptosis of U266 cells via PI3K/Akt-mTOR signaling pathways.
authors.affiliation: Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuan, Hebei 050000, P.R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Feng
authors.affiliation: Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuan, Hebei 050000, P.R. China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Luo
authors.affiliation: Academy of Military Medical Sciences of the Chinese PLA, Beijing 100850, P.R. China.
authors.forename: Ximin
authors.initials: X
authors.lastname: Guo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002867:Chromones / Q000494:pharmacology; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D000077385:Silybin; D012838:Silymarin / Q000737:chemistry / Q000494:pharmacology*; D035381:TATA-Binding Protein Associated Factors / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002867:Chromones; D009025:Morpholines; D009687:Nuclear Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D000077385:Silybin; D012838:Silymarin; D035381:TATA-Binding Protein Associated Factors; D058570:TOR Serine-Threonine Kinases; C403808:ABT1 protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C546842:MTOR protein, human