Coptisine regulates mitochondrial stress in cancer-associated fibroblasts via the ATF4/TRIB3 signalling axis to suppress lung nodule carcinoma

This study investigated whether berberine inhibits lung nodule carcinoma by regulating mitochondrial stress in cancer-associated fibroblasts (CAFs) and explored the underlying mechanisms. An orthotopic lung cancer mouse model was established. In ex vivo experiments, primary lung fibroblasts (PFCs) were co-cultured with Lewis lung carcinoma (LLC) cells to simulate the TME (Tumor Microenvironment). Cell viability, migration, invasion, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) levels were assessed. The results demonstrated that berberine inhibited lung nodule formation in a concentration-dependent manner, improved respiratory function, downregulated CAF markers, suppressed the epithelial-mesenchymal transition (EMT) process, elevated MMP, and reduced ROS levels. Mechanistically, berberine alleviated mitochondrial stress in CAFs via the ATF4/TRIB3 signaling axis, thereby inhibiting the malignant behavior of LLC cells. The study indicates that berberine mitigates mitochondrial stress in CAFs through the ATF4/TRIB3 axis, blocks CAF activation and its interaction with lung cancer cells, and ultimately suppresses lung nodule carcinoma.