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[2-deoxyglucose inhibits angiogenesis of rheumatoid arthritis via activating AMPK pathway]

Ying Wang1, Yingmei Wei1, Xiu Cheng1

  • 1Faculty of Pharmacy, Bengbu Medical College, Bengbu 233000, China.

Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University
|September 7, 2018
PubMed
Abstract

Insights

2-deoxyglucose (2-DG) effectively inhibits synovial pannus in adjuvant arthritis rats. It also suppresses human umbilical vein endothelial cell (HUVEC) proliferation, migration, and tube formation by activating the AMPK pathway and reducing Bcl-2 expression.

Area of Science:

  • Biomedical Science
  • Pharmacology
  • Cell Biology

Background:

  • Adjuvant arthritis is characterized by synovial pannus formation.
  • Angiogenesis plays a crucial role in the development of synovial pannus.
  • Inhibiting angiogenesis is a potential therapeutic strategy for adjuvant arthritis.

Purpose of the Study:

  • To investigate the anti-angiogenic effects of 2-deoxyglucose (2-DG) on synovial pannus in adjuvant arthritis rats.
  • To explore the underlying mechanisms of 2-DG's anti-angiogenic activity, focusing on endothelial cell behavior and signaling pathways.

Main Methods:

  • Histopathological analysis (HE staining) of synovial pannus in adjuvant arthritis rats treated with 2-DG.
  • In vitro assays including CCK-8 for HUVEC proliferation, Transwell for FLS migration, and Matrigel assay for HUVEC tube formation.
  • Western blot analysis to detect p-AMPK and Bcl-2 expression.
  • Inhibition of the AMPK signaling pathway using Compound C.

Main Results:

  • 2-DG treatment significantly reduced synovial pannus formation in vivo (P < 0.01).
  • In vitro, 2-DG inhibited HUVEC proliferation, migration, and tube formation (P < 0.01 or P < 0.001).
  • These anti-angiogenic effects were reversed by Compound C, indicating AMPK pathway involvement.
  • 2-DG increased p-AMPK and decreased Bcl-2 expression in HUVECs (P < 0.05).

Conclusions:

  • 2-deoxyglucose exhibits anti-angiogenic properties relevant to adjuvant arthritis.
  • The mechanism involves the activation of the AMPK signaling pathway.
  • Downregulation of Bcl-2 expression is associated with 2-DG's anti-angiogenic effects.
Keywords:
2-deoxyglucoseAMPK pathwayangiogenesisglycolysisrheumatoid arthritis

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