Ifebemtinib and paclitaxel synergistically inhibit the proliferation and metastasis of TNBC by blocking PI3K/Akt...

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Triple-negative breast cancer (TNBC) is aggressive with limited treatment options.
• Focal Adhesion Kinase (FAK) is upregulated in breast cancer, correlating with poor prognosis.
• There is a critical need for novel therapeutic strategies targeting TNBC.

Purpose of the Study:

• To investigate the efficacy of combining FAK inhibitor Ifebemtinib with paclitaxel in TNBC.
• To elucidate the molecular mechanisms underlying the combination therapy's effects.
• To evaluate FAK as a potential therapeutic target in TNBC.

Main Methods:

• In vitro studies using TNBC cell lines to assess proliferation, colony formation, cell cycle, apoptosis, and migration.
• In vivo studies in mouse models to evaluate tumor growth and lung metastasis.
• Western blotting and gene expression analysis to investigate molecular signaling pathways (FAK, PI3K/Akt, LSD1).

Main Results:

• Ifebemtinib and paclitaxel synergistically inhibited TNBC cell proliferation, colony formation, and induced G2/M cell cycle arrest and apoptosis.
• The combination suppressed TNBC cell migration and in vivo proliferation and lung metastasis.
• Mechanistically, the combination inhibited FAK phosphorylation and upregulated PIK3IP1 by downregulating LSD1, thereby blocking the PI3K/Akt pathway.

Conclusions:

• The combination of Ifebemtinib and paclitaxel demonstrates significant anti-tumor activity against TNBC.
• Targeting FAK and modulating the PI3K/Akt pathway via PIK3IP1 upregulation are key mechanisms of action.
• FAK inhibition represents a promising therapeutic strategy for TNBC treatment.