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Published on: February 23, 2019
[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.
Objective:
To explore the effect of arsenic trioxide (As2 O3) on the level of VEGF, VEGFR and the activity of MMP-2, 9 in K562 cells.
Methods:
The inhibition ratio of K562 cell was detected by MTT assay, the level of VEGF by Enzyme-linked immunosorbent assay (ELISA), the expression ratio of VEGFR by flow cytometry (FCM), and the activity of MMP-2, 9 by gelatin zymography assay.
Results:
(1) The IC50 of K562 cells was (2.12 +/- 0.11) micromol/L. Proliferation of K562 cells was significantly inhibited at the concentration of 0.4 - 6.4 micromol/L As2 O3 (P < 0.05). (2) The expression of VEGF was slightly up-regulated by 0.05 micromol/L As2 O3 (P > 0.05) and prominently inhibited by 0.4 micromol/L and 3.2 micromol/L As2 O3 (P < 0.05). As2 O3 had no influence on VEGFR. (3) The activity of MMP-2 and 9 was partly inhibited by 0.05 micromol/L As2 O3 incubated 72 hours and by 0.4, 3.2 micromol/L, As2 O3. With the increase of As2 O3 concentration and the incubation time, the inhibited effect on MMP-2 and 9 was enhanced.
Conclusions:
As2 O3 may down-regulate the expression of VEGF and inhibit the activity of MMP-2 and 9.
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.

