Ganoderic acid A suppresses autophagy by regulating the circFLNA/miR-486-3p/CYP1A1/XRCC1 axis to strengthen the sensitivity of lung cancer cells to cisplatin.

This article investigates the role of ganoderic acid A (GA-A), a bioactive compound from the traditional Chinese medicine Ganoderma lucidum, in enhancing the sensitivity of lung cancer cells to cisplatin (DDP) chemotherapy. The study demonstrates that GA-A suppresses autophagy—a cellular degradation process—by regulating the circFLNA/miR-486-3p/CYP1A1/XRCC1 molecular axis, thereby inhibiting viability, migration, invasion, and promoting apoptosis in both cisplatin-sensitive and cisplatin-resistant lung cancer cell lines (A549 and A549/DDP). In vivo experiments using xenograft mouse models further confirm that GA-A, alone or combined with DDP, reduces tumor growth and modulates related gene and protein expressions consistent with autophagy inhibition and enhanced chemosensitivity. These findings suggest GA-A as a potential therapeutic agent to overcome cisplatin resistance in lung cancer by targeting autophagy through specific noncoding RNA-mediated pathways.