Cannabidiol suppresses proliferation and induces cell death, autophagy and senescence in human cholangiocarcinoma cells via the PI3K/AKT/mTOR pathway

Abstract

CBD effectively inhibited CCA cell proliferation, suppressed colony formation and induced G0/G1 phase cell cycle arrest. Morphological examination revealed lipid droplets/vesicles in CCA cell lines. CBD induced autophagy by upregulating LC3BII, downregulating p62, and inhibiting the <i>p</i>-PI3K, <i>p</i>-AKT, and <i>p</i>-mTOR pathways. Additionally, CBD disrupted mitochondrial homeostasis by elevating ROS, reducing membrane potential, and induced cellular senescence by increasing the expression of p53 and p21. <i>In-vitro</i> results were confirmed by xenograft models. Overall, CBD suppresses proliferation and induces cell death, autophagy and senescence in CCA cells via the PI3K/AKT/mTOR pathway, which indicates a therapeutic option for CCA treatment.