[Relationship of PTEN/PI3K/AKT Signaling Pathway Protein Expression with Apoptosis and Drug-resistance of Children's ALL Primary Cells Treated with Daunorubicin]

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2019 Aug;27(4):1053-1057. doi: 10.19746/j.cnki.issn.1009-2137.2019.04.010.
[Article in Chinese]

Abstract

Objective: To investigate the relationship of PTEN/PI3K/AKT signaling pathway protein expression with apoptosis and drug-resistance of children's ALL primary cells treated with daunorubicin (DNR).

Methods: The bone marrow mononuclear cells in newly diagnosed and untreated B-ALL children were collected and cultured. After the treatment of primary-cultured cells with DNR of final concentration 0.5 mg/L for 24 h, the cell apoptosis rate was detected by using cell apoptosis assay kit; the samples were collected at the on test of culture and after drug treatment, then expression levels of PTEN, PI3K and AKT proteins were detected by Western blot, moreover the interindex correlation was analyzed.

Results: After DNR treatment, the apoptosis rate in PTEN low expression group was lower than that in PTEN high expression group (P<0.05), showing high positive correlation of the cell apoptosis rate with the expression of PTEN before DNR treatment; the cell apoptosis rate in PI3K and AKT low expression group was higher than that in PI3K and AKT high expression group (P<0.01); however, the expression of PI3K and AKT proteins was down-regulated after treatment with DNR (P<0.01).

Conclusion: The difference of PTEN expression is present in primary cells of B-ALL children, however the change of PTEN expression is not significant after DNR treatment, suggesting that the PTEN expression correlates with DNR-resistance. The DNR can induce the apoptosis of childrens B-ALL primary cells by down-regulating the expression of PI3K and AKT signaling pathway proteins.

题目: PTEN/PI3K/AKT信号通路与儿童急性淋巴细胞白血病原代细胞凋亡耐药的相关性.

目的: 探讨儿童急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)原代细胞中PTEN/PI3K/AKT信号通路蛋白表达与细胞凋亡和柔红霉素(daunorubicin,DNR)耐药的关系.

方法: 分离45例初诊未治儿童急性B系ALL(B-ALL)骨髓单个核细胞进行原代细胞培养,用终浓度0.5 mg/L的DNR干预24 h后使用细胞凋亡试剂盒检测凋亡率;于培养开始时和药物干预完成后取标本应用Western blot方法检测PTEN、PI3K、AKT蛋白表达水平,并进行各检测指标间的相关性分析.

结果: DNR干预后,PTEN低表达组凋亡率较PTEN高表达组低(P<0.05),显示凋亡率与干预前PTEN表达呈强正相关;PI3K-AKT低表达组凋亡率较PI3K-AKT高表达组高(P<0.01);DNR干预后PI3K-AKT蛋白表达降低(P<0.01).

结论: 儿童B-ALL原代细胞中PTEN表达存在差异,DNR干预后PTEN表达变化不显著,提示PTEN表达与DNR耐药相关。DNR可通过下调PI3K-AKT信号通路蛋白表达,诱导儿童B-ALL原代细胞凋亡.

MeSH terms

  • Apoptosis
  • Child
  • Daunorubicin
  • Humans
  • PTEN Phosphohydrolase
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Signal Transduction*

Substances

  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Daunorubicin