Abstract：OBJECTIVE: To investigate whether proteasome inhibitor MG-132 induces apoptosis of human erythroleukemia cell line K562 and possible mechanisms. METHODS: K562 cells were incubated with RPMI 1640 and exposed to 0, 1, 5, 10, 15 μmol/L of MG-132 for 24 hrs, respectively. The apoptosis of cells were detected by fluorescence microscope, DNA fragments and flow cytometry. The NF-κB mRNA expression was quantified by reverse transcription-polymerase chain reaction (RT-PCR). Expression of NF-κB and caspase-3 was semiquantitatively analyzed with SABC techniques. Caspase-3 activities were measured with a colorimetric method. RESULTS: The growth of K562 cells was inhibited and the apoptosis of the cells increased after MG-132 treatment in a dose-dependent manner. After 24 hrs of 15 μmol/L MG-132 treatment, the percentage of apoptotic cells (26.5±0.6%) increased significantly when compared with the untreated controls (1.2±0.1%) (P<0.01). MG-132 treatment decreased the mRNA and protein expression of NF-κB, and increased the protein expression of caspase-3. CONCLUSIONS: MG-132 can induce apoptosis of human erythroleukemia cell line K562 through the down-regulation of NF-κB expression and up-regulation of caspase-3 expression.［Chin J Contemp Pediatr, 2009, 11 (4):255-258］
WANG Xi-Ge,HAO Qing-Fei,TANG You-Cai. Induction of apoptosis by proteasome inhibitor MG-132 in human erythroleukemia cell line K562[J]. CJCP, 2009, 11(04): 255-258.
［1］Marx J. Cell biology. Ubiquitin lives up to its name ［J］.Science, 2002, 297(5588):1792-1794.
［2］Cervello M, Giannitrapani L, La Rosa M, Notarbartolo M, Labbozzetta M, Poma P, et al. Induction of apoptosis by the proteasome inhibitor MG132 in human HCC cells: Possible correlation with specific caspase-dependent cleavage of beta-catenin and inhibition of beta-catenin-mediated transactivation ［J］. Int J Mol Med, 2004, 13(5):7412748.
［3］Karin M, Cao Y, Greten FR, Li ZW. NF-kappaB in cancer: from innocent bystander to major culprit ［J］. Nat Rev Cancer, 2002, 2(4):301-310.
［4］Bladé J, Cibeira MT, Rosinol L. Bortezomib: a valuable new antineoplastic strategy in multiple myeloma［J］. Acta Oncol, 2005, 44(5):440-448.
［5］Smith GG. Proteasome inhibition in cancer therapy［J］. J Infus Nurs, 2005, 28(4):258-264.
［6］Hochwald SN, Lind DS, Malaty J, Copeland EM 3rd, Moldawer LL, MacKay SL. Antineoplastic therapy in colorectal cancer through proteasome inhibition［J］.Am Surg, 2003, 69(1):15-23.
［9］Kim DS, Kim SY, Jeong YM, Jeon SE, Kim MK, Kwon SB, et al. Light-activated indole-3-acetic acid induces apoptosis in g361 human melanoma cells［J］. Biol Pharm Bull, 2006, 29(12):2404-2409.
［10］Rajkumar SV, Richardson PG, Hideshima T, Anderson KC. Proteasome inhibition as a novel therapeutic target in human cancer ［J］.J Clin Oncol, 2005, 23(3):630-639.
［11］Guzman ML, Neering SJ, Upchurch D, Grimes B, Howard DS, Rizzieri DA, et al. Nuclear factor-kappaB is constitutively activated in primitive human acute myelogenous leukemia cells ［J］.Blood, 2001, 98(8):2301-2307.
