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Cimigenoside enhances Taxol chemosensitivity in triple-negative breast cancer via the γ-secretase/RBPJ-PXR axis.

Mei Feng1, Xin Yang2, Kuo Yao1

  • 1Department of Pathology and Pathophysiology, School of Basic Medical Sciences, Shenyang Medical College, Shenyang, China.

British Journal of Pharmacology
|April 4, 2026
PubMed
Summary
This summary is machine-generated.

Cimigenoside (CG) enhances Taxol effectiveness in triple-negative breast cancer (TNBC) by inhibiting the γ-secretase/RBPJ-PXR pathway. This natural compound overcomes Taxol resistance, improving therapeutic outcomes for TNBC patients.

Keywords:
chemosensitivitycimigenosidetriple‐negative breast cancerγ‐secretase/RBPJ‐PXR axis

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Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • The γ-secretase/NICD-PXR/Notch pathway promotes Taxol resistance in triple-negative breast cancer (TNBC).
  • Inhibiting this pathway is a potential strategy to improve Taxol chemosensitivity in TNBC.
  • Cimigenoside (CG), from Cimicifuga dahurica, is identified as a γ-secretase inhibitor.

Purpose of the Study:

  • To investigate the dynamic interaction between CG and γ-secretase.
  • To evaluate CG's efficacy in enhancing Taxol sensitivity in TNBC models.
  • To elucidate the mechanism by which CG regulates the γ-secretase/RBPJ-PXR axis.

Main Methods:

  • Molecular dynamics simulations and in vitro enzyme assays to study CG-PSEN-1 interaction.
  • In vitro and in vivo experiments to assess CG's effect on TNBC proliferation, migration, invasion, and apoptosis.
  • Dual luciferase reporter assays, subcellular fractionation, and Western blotting to analyze the γ-secretase/RBPJ-PXR axis regulation.

Main Results:

  • CG binds to the presenilin-1 (PSEN-1) cavity, inhibiting γ-secretase activity.
  • CG significantly potentiates Taxol's anti-proliferative, anti-migratory, and anti-invasive effects, while promoting apoptosis in MDA-MB-231/Taxol cells.
  • CG enhances Taxol's efficacy against subcutaneous and metastatic TNBC tumors in vivo.
  • CG inhibits RBPJ transcriptional activity, disrupts RBPJ-PXR interaction, and downregulates PXR targets, thereby increasing TNBC sensitivity to Taxol.

Conclusions:

  • Cimigenoside (CG) effectively enhances Taxol chemosensitivity in triple-negative breast cancer (TNBC).
  • CG acts by inhibiting the γ-secretase/RBPJ-PXR signaling axis.
  • This mechanism offers a promising therapeutic strategy for overcoming Taxol resistance in TNBC.