Vitexin Inhibits TNBC Progression and Metastasis by Modulating Macrophage Polarization Through EGFR Signaling

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• Triple-negative breast cancer (TNBC) presents significant therapeutic challenges due to its aggressive nature and lack of targeted treatments.
• Tumor-associated macrophages (TAMs) are key players in TNBC progression, often adopting a pro-tumorigenic M2 phenotype.
• The therapeutic potential of vitexin, a natural compound, on TAMs in TNBC remains largely uninvestigated.

Purpose of the Study:

• To investigate the anti-cancer effects of vitexin on TNBC cells.
• To determine vitexin's role in modulating macrophage polarization (M1 vs. M2) within the tumor microenvironment.
• To elucidate the involvement of the EGFR/PI3K/AKT/mTOR signaling pathway in vitexin's mechanism of action.

Main Methods:

• In vitro assessment of vitexin's impact on TNBC cell proliferation and invasion (MDA-MB-231, BT549).
• Analysis of macrophage polarization markers and cytokine profiles following vitexin treatment.
• Evaluation of EGFR phosphorylation and downstream signaling pathway activation (PI3K/AKT/mTOR).
• In vivo studies using a TNBC xenograft model to assess tumor growth inhibition and TAM polarization.

Main Results:

• Vitexin significantly suppressed TNBC cell proliferation and invasion.
• Vitexin treatment promoted M1 macrophage polarization and inhibited M2 polarization, alongside inducing macrophage-derived anti-cancer mediators.
• Vitexin modulated the EGFR/PI3K/AKT/mTOR pathway, reducing EGFR phosphorylation.
• In vivo, vitexin inhibited tumor growth and shifted TAMs towards an M1 phenotype, demonstrating synergistic effects with doxorubicin.

Conclusions:

• Vitexin exhibits potent anti-cancer properties against TNBC by directly inhibiting cancer cells and reprogramming the tumor microenvironment.
• Vitexin's ability to promote M1 macrophage polarization and suppress M2 polarization offers a novel immunomodulatory therapeutic strategy for TNBC.
• Targeting the EGFR/PI3K/AKT/mTOR pathway is a key mechanism underlying vitexin's efficacy in TNBC, suggesting its potential as a therapeutic agent, possibly in combination therapy.