title: Effects of arsenic trioxide alone and in combination with bortezomib in multiple myeloma RPMI 8266 cells.
abstract: The aim of this study was to detect the efficiency of arsenic trioxide (ATO) alone or together with bortezomib to inhibit proliferation and induce apoptosis in a multiple myeloma (MM) RPMI 8266 cells. Mechanisms of action were also investigated. RPMI 8266 cells were treated with ATO alone and in combination with bortezomib for 24 hours, and cell viability was assessed by modified MTT. Annexin V-F1TC and PI staining was used to detect the apoptosis rate and cell cycling was investigated by flow cytometry, along with expression of cell surface death receptor-4(DR4) and death receptor-5 (DR5). Western blotting was applied to detect the expression of bcl-2, caspase-3, caspase-8, and caspase-9. As a result, the ATO combined with bortezomib group showed more inhibition of RPMI 8266 cell viability than the ATO group. Expression of DR4 and DR5 on the cell surfaces, and the apoptosis rate were increased after treatment by ATO alone or combined with bortezomib. The cells appeared to arrest in G2/M phase after treatment. Expression of bcl-2 was more significantly decreased in the combination group, and that of caspase-3, caspase-8 and caspase-9 was significantly increased as well. Therefore, bortezomib can enhance ATO actions to induce apoptosis in RPMI 8266 cells, with decrease in expression of bcl-2 and increase of caspase-3, caspase-8 and caspase-9 proteins.
authors.affiliation: Cancer Center, the First Hospital of Jilin University, Changchun, China E-mail : cuijiuwei@yahoo.com.
authors.forename: Aadil Yousif
authors.initials: AY
authors.lastname: Elmahi
authors.forename: Chao
authors.initials: C
authors.lastname: Niu
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Guan-Jun
authors.initials: GJ
authors.lastname: Wang
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Hao
authors.forename: Jiu-Wei
authors.initials: JW
authors.lastname: Cui
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage / Q000494:pharmacology*; D001897:Boronic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D000069286:Bortezomib; D020169:Caspases / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010087:Oxides / Q000008:administration & dosage / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D011719:Pyrazines / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001152:Arsenicals; D001897:Boronic Acids; D010087:Oxides; D019253:Proto-Oncogene Proteins c-bcl-2; D011719:Pyrazines; D000069286:Bortezomib; D020169:Caspases; D000077237:Arsenic Trioxide