[Effect of arsenic trioxide on VEGF/R and MMP-2, 9 expressed in K562 cells]

Yu Zhang1, Jian-Dong Zhang, Jian Gu

  • 1Clinic Medical College of Yangzhou University, Yangzhou Institute of Hematology, Yangzhou 225001, China.

Abstract

Insights

Arsenic trioxide (As2 O3) inhibits K562 cell proliferation and down-regulates VEGF expression. As2 O3 also inhibits the activity of matrix metalloproteinases MMP-2 and MMP-9.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm.
  • K562 cells are a human immortalized myelogenous leukemia cell line derived from a CML patient.
  • Vascular Endothelial Growth Factor (VEGF) and its receptor (VEGFR) play crucial roles in angiogenesis and tumor progression.
  • Matrix Metalloproteinases (MMPs), particularly MMP-2 and MMP-9, are involved in extracellular matrix degradation and metastasis.

Purpose of the Study:

  • To investigate the effects of arsenic trioxide (As2 O3) on K562 cell proliferation.
  • To determine the impact of As2 O3 on VEGF and VEGFR expression in K562 cells.
  • To evaluate the influence of As2 O3 on the activity of MMP-2 and MMP-9 in K562 cells.

Main Methods:

  • K562 cell inhibition ratio was assessed using MTT assay.
  • VEGF levels were quantified by Enzyme-linked immunosorbent assay (ELISA).
  • VEGFR expression was analyzed by flow cytometry (FCM).
  • MMP-2 and MMP-9 activity was measured using gelatin zymography assay.

Main Results:

  • Arsenic trioxide demonstrated significant inhibition of K562 cell proliferation with an IC50 of (2.12 ± 0.11) µmol/L.
  • VEGF expression was notably inhibited by As2 O3 at concentrations of 0.4 and 3.2 µmol/L, while VEGFR expression remained unaffected.
  • The activity of MMP-2 and MMP-9 was inhibited by As2 O3, with enhanced inhibition observed at higher concentrations and longer incubation times.

Conclusions:

  • Arsenic trioxide exhibits anti-proliferative effects on K562 cells.
  • As2 O3 treatment leads to down-regulation of VEGF expression.
  • Arsenic trioxide effectively inhibits the enzymatic activity of MMP-2 and MMP-9.