Resibufogenin and Oxaliplatin Synergistically Inhibit Diffuse Gastric Cancer by Inactivating the...

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Diffuse Gastric Cancer (DGC) is aggressive with poor prognosis.
• Oxaliplatin (OX) is a first-line treatment, but resistance occurs.
• Resibufogenin (RBF) shows anti-cancer effects, but its role in DGC is unknown.

Purpose of the Study:

• Investigate RBF's sensitizing effect on OX for DGC.
• Elucidate RBF's targets and mechanisms in DGC treatment.
• Explore potential for novel sensitizers and patentable innovations.

Main Methods:

• In vitro: MTT assay, flow cytometry, Western blotting, immunofluorescence.
• In vivo: Human DGC cell xenografts in mouse models.
• Assessed efficacy, safety, and molecular mechanisms.

Main Results:

• RBF inhibited DGC cell proliferation dose- and time-dependently.
• Combination of RBF and OX improved DGC cell sensitivity to OX.
• Synergistic induction of apoptosis and autophagy; inhibition of migration and invasion in vitro.
• In vivo, RBF+OX combination significantly inhibited DGC progression without toxicity.
• RBF inhibited FAK expression/activation; RBF+OX synergistically inhibited FAK/AKT/GSK3β phosphorylation, blocking β-catenin nuclear entry.

Conclusions:

• RBF suppresses FAK, enhancing OX efficacy in DGC.
• Combination therapy synergistically blocks the FAK/AKT/GSK3β/β-catenin pathway.
• This offers a novel strategy for DGC treatment and FAK inhibitor development.