title: Synergistic effect of panobinostat and bortezomib on chemoresistant acute myelogenous leukemia cells via AKT and NF-κB pathways.
abstract: In this study, we investigated the synergistic effects of panobinostat and bortezomib on adriamycin-resistant HL60/ADR cells and refractory acute myelogenous leukemia (AML) primary cells. Combination of both agents had synergistic cytotoxicity on these cells, and increased the sensitivity of HL60/ADR cells to adriamycin. Panobinostat plus bortezomib was shown to modulate multiple apoptotic and drug metabolic related molecules, including activation of caspases, down-regulation of XIAP, Bcl-2 and MRP1. These effects were likely to be mediated via inhibition of AKT and NF-κB pathways. These findings provide evidence for clinic protocols using panobinostat and borezomib to overcome drug resistance in refractory AML patients.
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Xue-Jie
authors.initials: XJ
authors.lastname: Jiang
authors.forename: Kai-Kai
authors.initials: KK
authors.lastname: Huang
authors.forename: Mo
authors.initials: M
authors.lastname: Yang
authors.forename: Liang
authors.initials: L
authors.lastname: Qiao
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Jie-Yu
authors.initials: JY
authors.lastname: Ye
authors.forename: Hong-Sheng
authors.initials: HS
authors.lastname: Zhou
authors.forename: Zheng-Shan
authors.initials: ZS
authors.lastname: Yi
authors.forename: Fu-Qun
authors.initials: FQ
authors.lastname: Wu
authors.forename: Zhi-Xiang
authors.initials: ZX
authors.lastname: Wang
authors.forename: Qing-Xia
authors.initials: QX
authors.lastname: Zhao
authors.forename: Fan-Yi
authors.initials: FY
authors.lastname: Meng
mesh_terms: D000107:Acetylation; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001897:Boronic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D000069286:Bortezomib; D020169:Caspases / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D018922:HL-60 Cells; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D000077767:Panobinostat; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D059748:Proteolysis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011719:Pyrazines / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D006877:Hydroxamic Acids; D007211:Indoles; D016328:NF-kappa B; D011719:Pyrazines; D000069286:Bortezomib; D000077767:Panobinostat; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D020169:Caspases