title: [CML cell apoptosis induced by AMN107 combined with heme oxygenase-1 inhibitor].
abstract: This study was aimed to investigate the effect of AMN107 (nilotinib) combined with heme oxygenase-1 (HO-1) inhibitor zinc protoporphyrin IX (ZnPPIX) on chronic myeloid leukemia (CML) cells and its mechanism. Proliferative rate of cells treated with AMN107 (10 µmol/L) and ZnPPIX (10 µmol/L) alone or both for different time was observed by MTT and trypan blue methods; the expression of HO-1 in the control group, ZnPPIX (10 µmol/L) group, AMN107 (10 µmol/L) group, AMN107 (10 µmol/L) combined with ZnPPIX (10 µmol/L) group was evaluated by semi-quantitative RT-PCR and Western blot at 48 h. Cell apoptosis was detected by flow cytometry with Annexin V/PI double staining at 48 h. The results showed that the strongest inhibition of cell proliferation was detected in combined group, and in a time-dependent manner; the expression level of HO-1 was lowest in combined group; the cell apoptosis rates were (11.38 ± 0.02)%, (17.44 ± 0.08)%, (39.81 ± 0.07)% and (56.46 ± 0.19)% in the control group, ZnPPIX group, AMN107 group, AMN107 combined with ZnPPIX group at 48 h respectively. It is concluded that the second-generation tyrosine kinase inhibitor AMN107 can induce the apoptosis in CML cells. Inhibition of HO-1 expression can enhance the killing effect of AMN107 on CML cells, which provides experimental evidence to further improve the clinical efficacy of CML treatment.
authors.affiliation: Department of Hematology, Guiyang Medical College, Guiyang, Guizhou Province, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.forename: Ji-Shi
authors.initials: JS
authors.lastname: Wang
authors.forename: Chang
authors.initials: C
authors.lastname: Ynag
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Yu
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Dan
authors.initials: D
authors.lastname: Ma
authors.forename: Qin
authors.initials: Q
authors.lastname: Fang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors*; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology; D011524:Protoporphyrins / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*
chemical_list: D011524:Protoporphyrins; D011743:Pyrimidines; C017803:zinc protoporphyrin; D051547:Heme Oxygenase-1; C498826:nilotinib