title: Upregulation of AIOLOS induces apoptosis and enhances etoposide chemosensitivity in Jurkat leukemia cells.
abstract: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive neoplastic disorder of immature hematopoietic precursors committed to T-cell lineage. T-ALL accounts for ~15% of pediatric ALL cases and is prone to early relapse. With new and improved treatment protocols, the prognosis of T-ALL has improved particularly in children; however, the outcome of relapsed T-ALL cases remains poor. The AIOLOS gene is necessary to control lymphocyte differentiation and may be a potential target of T-ALL therapy. In the present study, Jurkat cells were divided into three groups: untransfected (UT) control, lentiviral vector control (Lenti-Mock) and AIOLOS-overexpressing (Lenti-AIOLOS) groups. Lenti-AIOLOS Jurkat cells were constructed by lentiviral transduction; cell cycle analysis, apoptosis and cytotoxicity assays were then performed to evaluate the effects of AIOLOS on cell cycle distribution, apoptosis and cell chemosensitivity to etoposide of Jurkat cells in vitro. Moreover, the expression levels of genes associated with apoptosis and cell cycle were investigated by quantitative reverse transcription-polymerase chain reaction. Results showed that the percentage of Jurkat cells in the G0/G1 phase increased from 71.5 (UT) to 85.4% (Lenti-AIOLOS; P<0.05), yet the percentage of cells in the S-phase decreased from 15.1 (UT) to 11.6% (Lenti‑AIOLOS; P<0.05). The percentage of total apoptotic cells was significantly increased in the AIOLOS-transfected Jurkat cells (21.93%) compared with this percentage in the Lenti-Mock (13.35%) or the UT group (13.30%; P<0.05). Consistent with these results, AIOLOS overexpression induced P21 and P27 upregulation and CCND3 and SKP2 downregulation. Furthermore, AIOLOS overexpression synergistically increased the cytotoxic effects of etoposide and downregulated NF-κB expression. Our findings revealed that lentivirus-mediated AIOLOS overexpression in Jurkat cells induced cell apoptosis, arrested the cell cycle at the G0/G1 phase, and synergistically increased the sensitivity of Jurkat cells to etoposide by inhibiting NF-κB activity.
authors.affiliation: Department of Pediatrics, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhuang
authors.affiliation: Department of Pediatrics, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Pediatrics, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Nianzheng
authors.initials: N
authors.lastname: Sun
authors.affiliation: Department of Pediatrics, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Ju
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics*; D002454:Cell Differentiation / Q000276:immunology; D045744:Cell Line, Tumor; D056743:Cyclin D3 / Q000096:biosynthesis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000494:pharmacology*; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics*; D006801:Humans; D051740:Ikaros Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D019169:Jurkat Cells; D016086:Lentivirus / Q000235:genetics; D016328:NF-kappa B / Q000096:biosynthesis / Q000378:metabolism; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D044786:S-Phase Kinase-Associated Proteins / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C534696:CCND3 protein, human; D056743:Cyclin D3; D050759:Cyclin-Dependent Kinase Inhibitor p21; C106285:IKZF3 protein, human; D016328:NF-kappa B; D044786:S-Phase Kinase-Associated Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051740:Ikaros Transcription Factor; D005047:Etoposide