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(20S) Ginsenoside Rh2 Inhibits STAT3/VEGF Signaling by Targeting Annexin A2

Yu-Shi Wang1, Chen Chen1, Shi-Yin Zhang1

  • 1Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China.

International Journal of Molecular Sciences
|September 10, 2021
PubMed

Insights

The natural compound (20S) ginsenoside Rh2 inhibits signal transducers and activators of transcription 3 (STAT3) by blocking its interaction with Annexin A2. This natural STAT3 inhibitor reduces tumor cell growth and angiogenesis, showing potential for targeted cancer therapy.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Pharmacology

Background:

  • Signal transducers and activators of transcription 3 (STAT3) is crucial for gene expression, but its aberrant activation drives tumor growth and angiogenesis.
  • Tumor-associated protein Annexin A2 interacts with STAT3, promoting its phosphorylation and transcriptional activity, which are key in cancer progression.

Purpose of the Study:

  • To investigate the inhibitory effect of (20S) ginsenoside Rh2 (G-Rh2) on STAT3 activity in HepG2 cells.
  • To elucidate the mechanism by which G-Rh2 affects the interaction between Annexin A2 and STAT3.
  • To evaluate the potential of G-Rh2 as a targeted therapy agent.

Main Methods:

  • Investigated the effect of (20S) G-Rh2 on STAT3 activity and its interaction with Annexin A2 in HepG2 cells.
  • Assessed STAT3 Tyr705 phosphorylation and transcriptional activity.
  • Evaluated the impact of G-Rh2 on VEGF expression and HUVEC growth/migration in a co-culture system.
  • Utilized Annexin A2-K301A mutant to confirm the mechanism of action.

Main Results:

  • (20S) G-Rh2 inhibited STAT3 activity in HepG2 cells by interfering with the Annexin A2-STAT3 interaction.
  • G-Rh2 suppressed STAT3 Tyr705 phosphorylation and transcriptional activity, leading to decreased VEGF levels.
  • The reduction in VEGF impaired HUVEC growth and migration, suggesting anti-angiogenic effects.
  • G-Rh2's inhibitory effect on STAT3 was abolished in cells expressing a binding-deficient Annexin A2 mutant.

Conclusions:

  • (20S) G-Rh2 acts as a potent inhibitor of STAT3 through Annexin A2-mediated mechanisms.
  • G-Rh2 demonstrates significant potential for targeted cancer therapy by inhibiting tumor growth and angiogenesis.
  • The findings highlight G-Rh2 as a promising natural compound for therapeutic development in oncology.
Keywords:
(20S)G-Rh2Annexin A2STAT3VEGF

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