Decreased expression of the augmenter of liver regeneration results in growth inhibition and increased chemosensitivity of acute T lymphoblastic leukemia cells

Oncol Rep. 2017 Nov;38(5):3130-3136. doi: 10.3892/or.2017.5984. Epub 2017 Sep 21.

Abstract

Augmenter of liver regeneration (ALR) plays crucial roles in cell survival and growth. Previous studies have demonstrated that ALR exerts a protective effect on toxic agent‑induced cell death in acute T lymphoblastic leukemia cells and ALR knockdown can sensitize cancer cells to radiation. However, the biological functions of ALR against drug resistance in T-cell acute lymphoblastic leukemia are mostly unknown. In the present study, we investigated the effect of small interfering RNA (siRNA)-induced ALR silencing on cell proliferation and sensitivity to vincristine (VCR) of Jurkat cells. We found that ALR siRNA effectively decreased the ALR expression, then inhibited cell growth and increased sensitivity to VCR in Jurkat cells. Flow cytometry assay revealed that the downregulation of ALR expression promoted cell apoptosis and regulated cell cycle distribution. Following incubation with VCR, apoptosis-related proteins, such as pro-PARP, pro-caspase 8, pro-caspase 3 and Bcl-2 were downregulated in the siRNA/ALR group. Pretreatment with siRNA/ALR in combination with VCR resulted in prolonged G2/M arrest, accompanied by downregulation of cdc25c and cdc2 expression and dissociation of cyclin B1. In conclusion, the results of this study demonstrated that targeted inhibition of the ALR expression in Jurkat cells triggered cell growth inhibition and sensitized cells to VCR via promoting apoptosis and regulating the cell cycle.

MeSH terms

  • Apoptosis / drug effects*
  • Autophagy-Related Protein 5 / genetics
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cytochrome Reductases / antagonists & inhibitors
  • Cytochrome Reductases / genetics*
  • Drug Resistance, Neoplasm / genetics*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Knockdown Techniques
  • Humans
  • Jurkat Cells
  • Oxidoreductases Acting on Sulfur Group Donors
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • RNA, Small Interfering / genetics
  • Vincristine / administration & dosage*
  • Vincristine / adverse effects

Substances

  • Autophagy-Related Protein 5
  • RNA, Small Interfering
  • Vincristine
  • Cytochrome Reductases
  • GFER protein, human
  • Oxidoreductases Acting on Sulfur Group Donors