Coptisine suppresses pulmonary nodule carcinogenesis by inducing mitochondrial apoptosis in cancer-associated fibroblasts via inhibition of the PI3K/AKT/mTOR pathway

Abstract

Coptisine, a bioactive compound derived from Coptis chinensis, exerts anticancer effects by inducing mitochondrial-mediated apoptosis in primary pulmonary fibroblasts (PFCs) and inhibiting tumor-supportive cytokines. This study investigated the role of Coptisine in the malignant transformation of pulmonary nodules and its underlying mechanisms. Using an orthotopic lung cancer model and an ex vivo co-culture system, we found that Coptisine significantly inhibited tumor growth and improved pulmonary function. Experimental results demonstrated that Coptisine treatment reduced the expression of the tumor cell proliferation marker Ki67, while decreasing the levels of cancer-associated fibroblast markers α-SMA and FAP. At the molecular level, Coptisine modulated the balance of apoptosis-related proteins, characterized by the downregulation of the anti-apoptotic protein BCL-2 and the upregulation of the pro-apoptotic protein Bax. Furthermore, this compound significantly reduced the secretion of multiple pro-tumorigenic factors, including TGF-β, VEGF, and IL-6.These findings demonstrate that berberine exerts anti-tumor effects by targeting the tumor microenvironment, highlighting its potential as a therapeutic agent for early-stage lung cancer. By inducing mitochondrial apoptosis in cancer-associated fibroblasts (CAFs), it disrupts the tumor-supporting microenvironment, thereby providing a novel therapeutic strategy for pulmonary nodules.