title: [Effects of sorafenib on proliferation and apoptosis of human multiple myeloma cell RPMI 8226].
abstract: This study was aimed to investigate the effects of sorafenib on proliferation and apoptosis of MM cell line RPMI-8226, and to explore the its potential anti-tumor mechanism. The inhibitory rate of multiple myeloma cell proliferation was tested by MTT. Transmission electron microscopy was used to observe morphological and ultrastructural changes of RPMI-8226 cells treated with sorafenib. The effects of sorafenib on the apoptosis and cell cycle of RPMI-8226 cells was detected by flow cytometry. The effects of sorafenib on the expression of caspase-3, BCL-2 and MCL-1 mRNA and protein were assayed by RT-PCR and Western blot respectively. The results showed that sorafenib (0-10.0 µmol/L) could obviously inhibit the proliferation of RPMI-8226 cells in time and dose-dependent manner. Flow cytometry results showed that sorafenib could induce apoptosis of RPMI-8226 cells, the difference was statistical significance (P < 0.05). Sorafenib mainly arrested RPMI-8226 cells in the G1 phase (P < 0.05). Typical apoptotic morphological and ultrastructural changes of MM cells could be observed under transmission electron microscope, Examination of cellular signaling pathways showed that sorafenib induced upregulation of cleaved-caspase-3 expression, and simultaneous downregulation of BCL-2 and MCL-1 expression. It is concluded that sorafenib displays anti-myeloma activity. Activating the death receptor pathway and arresting cell cycle may be two of the relatated mechanisms.
authors.affiliation: Department of Hematology, Tangdu Hospital of Fourth Military Medical University, Xi'an 710038, Shaanxi Province, China.
authors.forename: Nai-Cen
authors.initials: NC
authors.lastname: Zhou
authors.affiliation: Department of Hematology, The First Hospital, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Bao-Lan
authors.initials: BL
authors.lastname: Liu
authors.affiliation: Department of Hematology, The First Hospital, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Mei-Ying
authors.initials: MY
authors.lastname: Qi
authors.affiliation: Department of Hematology, The First Hospital, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Hematology, The First Hospital, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy / Q000473:pathology*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2; D015398:Signal Transduction; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D019253:Proto-Oncogene Proteins c-bcl-2; D009536:Niacinamide; D000077157:Sorafenib; D053148:Caspase 3