title: [Mechanism of HL-60 cells apoptosis induced by proteasome inhibitor MG132].
abstract: The purpose of this study was to elucidate the apoptosis, apoptotic pathway of HL-60 cells induced by proteasome inhibitor MG132 and its effect on allogeneic mixed lymphocyte reaction. Apoptosis of HL-60 cells was detected by flow cytometry, the expression of P21, P27 and P53 proteins in HL-60 cells treated with MG132 was assayed by Western blot. The HL-60 cells were treated with 1 µmol/L MG132 for 48 h, and irradiated by 75 Gy of (60)Co γ-ray, but their antigenicity was preserved. The effect of irradiated HL-60 cells treated with MG132 on proliferation of peripheral blood mononuclear cells (PBMNC) was measured by CCK-8 method. The results showed that the apoptotic rate of MG132-treated HL-60 cells increased in dose-and time-dependent manner. No significant changes in MG132-induced apoptosis were observed after inhibiting caspase-8 and caspase-9 pathway. The expression of P21 and P27 protein increased after treatment of HL-60 cells with MG132. CCK-8 test showed that HL-60 cells induced with low-dose of MG132 displayed the enhancing effect on proliferation of PBMNC. It is concluded that high dose of MG132 can induce the apoptosis of HL-60 cells, and has direct killing effect on HL-60 cells, but this inducing apoptotic effect on HL-60 cells can not be realized through caspase-8 and caspase-9 pathway. The P21 and P27 protein may be involved in MG132 induced HL-60 cell apoptosis. Low dose of MG132 promotes the proliferation of PBMNC in healthy individuals and enhance the immunity of organism.
authors.affiliation: Department of Hematology, Tianyou Hospital Affiliated to Wuhan University of Science and Technology, Wuhan 430064, China.
authors.forename: Yong-Ming
authors.initials: YM
authors.lastname: Zhou
authors.forename: Mei-Xia
authors.initials: MX
authors.lastname: Yu
authors.forename: Yu-Zhen
authors.initials: YZ
authors.lastname: Qiu
authors.forename: Xiao-Lei
authors.initials: XL
authors.lastname: Xing
authors.forename: Chun-Hong
authors.initials: CH
authors.lastname: Yao
authors.forename: Ru-Jun
authors.initials: RJ
authors.lastname: Bai
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology*; D061988:Proteasome Inhibitors / Q000494:pharmacology*
chemical_list: C493956:CDKN1A protein, human; C436291:CDKN1B protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D007976:Leupeptins; D061988:Proteasome Inhibitors; D050760:Cyclin-Dependent Kinase Inhibitor p27; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde