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Ginsenoside Rh2 regulates triple-negative breast cancer proliferation and apoptosis via the IL-6/JAK2/STAT3 pathway

Rumeng Ding1, Quancheng Kan1, Ting Wang1

  • 1Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Frontiers in Pharmacology
|January 23, 2025
PubMed
Abstract

Insights

Ginsenoside Rh2 inhibits triple-negative breast cancer (TNBC) growth by suppressing the IL-6/JAK2/STAT3 pathway. This study reveals key molecular mechanisms for ginsenoside Rh2

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Pharmacology

Background:

  • Triple-negative breast cancer (TNBC) presents significant therapeutic challenges.
  • Ginsenoside Rh2 shows promise in inducing apoptosis in TNBC cells, but its mechanisms are unclear.
  • Understanding ginsenoside Rh2's molecular targets is crucial for its therapeutic application in TNBC.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which ginsenoside Rh2 regulates apoptosis and proliferation in TNBC.
  • To identify key molecular targets and signaling pathways involved in ginsenoside Rh2's anti-TNBC effects.
  • To provide new insights into the therapeutic potential of ginsenoside Rh2 for TNBC treatment.

Main Methods:

  • Network analysis and transcriptome sequencing to identify potential targets.
  • In vivo imaging and immunohistochemistry in a TNBC mouse model.
  • Functional assays, ELISA, Western blot, and qRT-PCR to assess cellular effects and molecular mechanisms.

Main Results:

  • Network analysis identified 47 common targets, with GO enrichment suggesting roles in apoptosis, proliferation, and kinase activity.
  • The JAK/STAT signaling pathway, specifically the IL-6/JAK2/STAT3 axis, was identified as a key mechanism.
  • Ginsenoside Rh2 inhibited tumor growth in vivo and reduced key proteins (IL-6, IL-6R, STAT3, Bcl-2, Bcl-xL) and kinases (AMPK-α1, PKA-Cα) in TNBC.

Conclusions:

  • Ginsenoside Rh2 effectively regulates TNBC proliferation and apoptosis by suppressing the IL-6/JAK2/STAT3 pathway.
  • Findings were validated both in vitro and in vivo, confirming the pathway's central role.
  • This study significantly advances the understanding of ginsenoside Rh2's therapeutic potential against TNBC.
Keywords:
IL-6/JAK2/STAT3 pathwayapoptosisginsenoside Rh2network Pharmacologytriple-negative breast cancer

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