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SB218078 inhibits angiogenesis and epithelial-mesenchymal transition in breast cancer

Qianxue Wu1, Jiawei Xu2, Xin Tang3

  • 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Frontiers in Pharmacology
|March 31, 2025
PubMed
Abstract

Insights

SB218078 dual-targets tumor angiogenesis and epithelial-mesenchymal transition (EMT) in breast cancer by inhibiting the Chk1/ZEB1 axis. This novel approach offers a promising therapeutic strategy with reduced adverse effects compared to VEGFR2 inhibitors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) inhibitors face clinical challenges due to adverse effects.
  • Tumor angiogenesis and epithelial-mesenchymal transition (EMT) are critical processes in breast cancer progression.
  • Novel therapeutic strategies are needed to target both angiogenesis and EMT simultaneously.

Purpose of the Study:

  • To evaluate the novel compound SB218078 as a dual-targeting agent against breast cancer angiogenesis and EMT.
  • To elucidate the mechanism of action of SB218078, focusing on the Chk1/ZEB1 signaling pathway.

Main Methods:

  • In vitro assays assessed SB218078's anti-angiogenic effects on endothelial cells.
  • In vivo studies utilized zebrafish angiogenesis models and mouse xenografts for breast cancer progression.
  • Mechanistic investigations involved the Chk1/ZEB1 signaling axis with genetic interventions.

Main Results:

  • SB218078 suppressed angiogenesis in vitro and in vivo, and reduced breast cancer cell aggressiveness and tumor growth.
  • SB218078 selectively inhibited ZEB1, a key EMT transcription factor, via Chk1 inhibition.
  • ZEB1 knockdown mimicked SB218078's anti-angiogenic effects, while ZEB1 overexpression reversed them.

Conclusions:

  • SB218078 demonstrates dual-action therapeutic potential by blocking both angiogenesis and EMT in breast cancer.
  • The Chk1-ZEB1 axis is the key mechanism underlying SB218078's dual activity.
  • SB218078 represents a promising novel strategy distinct from traditional VEGFR2 inhibitors, warranting further preclinical development.
Keywords:
EMTSB218078ZEB1angiogenesisbreast cancer

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