title: [Mechanism of apoptosis synergistically induced by bortezomib combined with cytarabine in U937 cell line].
abstract: This study was aimed to further explore the apoptosis-inducing effect of bortezomib combined with cytarabine (Ara-C) on U937 cell line. Proliferation and apoptosis in U937 cells treated with bortezomib and/or Ara-C were assessed by cell count. Cell cycle distribution and reactive oxygen species (ROS) production level were measured by using flow cytometry. Cell signaling pathway related to apoptosis was analyzed by Western blot. The results showed that 10 nmol/L bortezomib combined with 50 nmol/L Ara-C significantly inhibited U937 cell proliferation. These two drug combination synergistically induced apoptosis in U937 cells, significantly increased cellular ROS level, and up-regulated the expression of phosphorylated form of JNK and P38 and down-regulated phosphorylation of ERK. It is concluded that the apoptosis of U937 cells synergistically induced by bortezomib combined with low concentration Ara-C is possibly associated with up-regulation of phosphorylated form of JNK, P38 and down-regulation of phosphorylation of ERK induced by increase of ROS, resulting in decrease of mitochondrial potential.
authors.affiliation: National Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
authors.forename: Cong
authors.initials: C
authors.lastname: He
authors.forename: Xin
authors.initials: X
authors.lastname: DU
authors.forename: Sheng-Hong
authors.initials: SH
authors.lastname: DU
authors.forename: Pei-Min
authors.initials: PM
authors.lastname: Jia
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Tong
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D003561:Cytarabine / Q000494:pharmacology*; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System; D010766:Phosphorylation; D011719:Pyrazines / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020298:U937 Cells
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D017382:Reactive Oxygen Species; D003561:Cytarabine; D000069286:Bortezomib