title: [Effect of ADAM10 Inhibitor GI254023X on Proliferation and Apoptosis of Acute T-Lymphoblastic Leukemia Jurkat Cells In Vitro and Its Possible Mechanisms].
abstract: OBJECTIVE
  To investigate the effect of ADAM10 inhibitor GI254023X on the proliferation and apoptosis of acute T-lymphoblastic leukemia Jurkat cells and its mechanisms.
  
  
  METHODS
  Jurkat cells were treated with different concentrations of GI254023X, the proliferation-inhibition curve was assayed and plotted by CCK-8 method, the cell viability and apoptosis was detected by flow cytometry with Annexin V and 7-AAD staining, the cleavage of Notch1 protein was determined by Western blot, the transcripts of anti-apoptotic genes BCL-2, MCL-1, BCL-xl and Notch1 target gene Hes-1 were detected by real-time PCR.
  
  
  RESULTS
  The GI254023X obviously inhibited the proliferation of Jurkat cells in concentration-dependent manner. As compared with the control group, the apoptosis of cells increased along with increment of GI254023X concentration. Compared with control group, the expression of Cleaved Notch1 was down-regulated while the expression of Notch1 was up-regulated in a time-dependent manner after the treatment with GI254023X. The levels of MCL-1 and Hes-1 mRNA transcripts in Jurkat cells were reduced in GI254023X treated group, but did not show obvious effect on the level of BCL-2 and BCL-xl mRNA transcripts.
  
  
  CONCLUSIONS
  GI254023X can remarkably inhibit proliferation and induce apoptosis of Jurkat cells. The inhibition of Notch1 activation and the down-regulation of apoptosis-related gene MCL-1 may be involved in the process of apoptosis.
authors: Institution of Hematology, Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China.|Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China.
authors: Sha
authors: S
authors: Ma
authors: Institution of Hematology, Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China.
authors: Jie
authors: J
authors: Xu
authors: Institution of Hematology, Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China.|Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China.
authors: Xue
authors: X
authors: Wang
authors: Institution of Hematology, Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China.
authors: Qing-Yun
authors: QY
authors: Wu
authors: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China.
authors: Jiang
authors: J
authors: Cao
authors: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China.
authors: Zheng-Yu
authors: ZY
authors: Li
authors: Institution of Hematology, Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China.|Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China.
authors: Ling-Yu
authors: LY
authors: Zeng
authors: Institution of Hematology, Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China.|Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China. E-mail: chenchong@xzmc.edu.cn.
authors: Chong
authors: C
authors: Chen
authors: Institution of Hematology, Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China.|Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China. E-mail: lihmd@163.com.
authors: Kai-Lin
authors: KL
authors: Xu
mesh_terms: D051722:ADAM Proteins; D000072197:ADAM10 Protein; D053829:Amyloid Precursor Protein Secretases; D017209:Apoptosis; D049109:Cell Proliferation; D004151:Dipeptides; D015536:Down-Regulation; D006801:Humans; D006877:Hydroxamic Acids; D066298:In Vitro Techniques; D019169:Jurkat Cells; D008565:Membrane Proteins; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; D051881:Receptor, Notch1
chemical_list: C555398:3-(formylhydroxyamino)-2-(3-phenyl-1-propyl)butanoic acid (2,2-dimethyl-1-methylcarbamoyl-1-propyl)amide; D004151:Dipeptides; D006877:Hydroxamic Acids; D008565:Membrane Proteins; D051881:Receptor, Notch1; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human