[Acadesine Inhibits the Proliferation of K562 Cells and Enhances their Sensitivity to Imatinib]

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2016 Feb;24(1):36-40. doi: 10.7534/j.issn.1009-2137.2016.01.007.
[Article in Chinese]

Abstract

Objective: To investigate the effects of AMPK agonist Acadesine (AICAR) on growth inhibition of K562 cells and their sensitivity to imatinib (IM).

Methods: K562 cells were cultured with different concentrations of AICAR alone or its combination with IM for 48 hours, the CCK-8 assay was used to detect cell proliferation, the cell cycle distribution and apoptosis were analyzed by flow cytometry. The expression levels of Cyclin D1, Cyclin E1 and Caspase 3 protein were determined by Western blot.

Results: AICAR inhibited the proliferation of K562 cells in dose-dependent manner, and their IC50 value was 0.45 mmol/L at 48 hours. AICAR could induce arrest of K562 cells in G1 phase and down-regulated the protein expression levels of Cyclin D1 and Cyclin E1; whereas it didn't influence the cell apoptosis. Additionally, the growth inhibition of cells induced by IM was enhanced by AICAR.

Conclusion: AICAR can inhibit the proliferation of K562 cells by arresting the cell cycle and enhancing the sensitivity of K562 cells to IM.

MeSH terms

  • Aminoimidazole Carboxamide / analogs & derivatives*
  • Aminoimidazole Carboxamide / pharmacology
  • Apoptosis
  • Caspase 3 / metabolism
  • Cell Cycle Checkpoints*
  • Cell Proliferation / drug effects*
  • Cyclin D1 / metabolism
  • Cyclin E / metabolism
  • Humans
  • Imatinib Mesylate / pharmacology*
  • K562 Cells / drug effects
  • Oncogene Proteins / metabolism
  • Ribonucleosides / pharmacology*

Substances

  • CCND1 protein, human
  • CCNE1 protein, human
  • Cyclin E
  • Oncogene Proteins
  • Ribonucleosides
  • Cyclin D1
  • Aminoimidazole Carboxamide
  • acadesine
  • Imatinib Mesylate
  • CASP3 protein, human
  • Caspase 3