Acyclic Retinoid Inhibits the EGFR/AKT Signaling Pathway and Cancels Cisplatin-resistant Cell Characteristics

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality.
• Overactivation of the EGFR/AKT pathway drives NSCLC progression.
• Cisplatin efficacy is limited by resistance and side effects.

Purpose of the Study:

• To investigate the efficacy of acyclic retinoid (ACR) in NSCLC.
• To determine if ACR inhibits EGFR/AKT signaling.
• To assess ACR's potential to enhance cisplatin therapy in NSCLC and resistant cells.

Main Methods:

• Treatment of NSCLC A549 and cisplatin-resistant A549 (A549CR) cells with ACR and cisplatin.
• Assessment of cell viability, apoptosis, and protein expression/phosphorylation (EGFR, AKT).
• Immunoblotting and cell viability assays were utilized.

Main Results:

• ACR reduced NSCLC cell viability and induced apoptosis.
• ACR inhibited EGFR/AKT signaling and upregulated p27^KIP1.
• ACR combined with cisplatin synergistically decreased viability and restored cisplatin sensitivity in resistant cells.

Conclusions:

• ACR demonstrates significant antitumor activity in NSCLC models.
• ACR enhances cisplatin efficacy by inhibiting EGFR/AKT signaling.
• ACR represents a potential therapeutic agent for NSCLC, including cisplatin-resistant cases.