Icariin mediates autophagy and apoptosis of hepatocellular carcinoma cells induced by the β-catenin signaling pathway through lncRNA LOXL1-AS1

To investigate the effect of icariin (ICA) on hepatocellular carcinoma (HCC) and its autophagy/apoptosis mechanism in HCC. The anti-HCC mechanism of ICA was investigated using HCC cells treated with 20 mu mol/L ICA. Cell viability and proliferation were assessed using CCK-8 and colony formation assays, respectively, while TUNEL staining evaluated anti-apoptotic effects. DHE staining quantified intracellular ROS levels, and JC-1 staining assessed mitochondrial membrane potential. The expression of LC3 was detected by immunofluorescence staining. Additionally, HepG2 cells (2.0 x 106) were implanted into the thymus of BALB/c nude mice, which received intraperitoneal injections of 40 mg/kg ICA. Western blotting was used to evaluate the expression of proteins related to apoptosis and autophagy. ICA effectively inhibited the proliferation and invasion of HCC cells, enhancing autophagy and apoptosis. Silencing of lncRNA LOXL1-AS1 reduced beta-catenin expression and downregulated PI3K/AKT/mTOR pathway phosphorylation. Targeting beta-catenin with siRNA augmented apoptosis in HepG2 cells through elevated levels of Bax and caspase-3/8/9 and boosted autophagy via increased expression of LC3-II, Atg5, Atg7, Atg8, and Beclin-1. ICA reversed this autophagic effect, while rapamycin enhanced ICA's efficacy. In vivo, ICA suppressed tumor growth and promoted autophagy and apoptosis in mice. Icariin induces autophagy and apoptosis in HCC cells via the beta-catenin signaling pathway mediated by lncRNA LOXL1-AS1, offering a novel approach to HCC clinical management.