Atractylodin inhibited the migration and induced autophagy in cholangiocarcinoma cells via PI3K/AKT/mTOR and p38MAPK signalling pathways

Objectives The effects of atractylodin (ATD), the bioactive compound from Atractylodes lancea, on migration and autophagy status of cholangiocarcinoma cell line were investigated. Methods Cytotoxic activity and effects on cell migration and invasion were evaluated by MTT and trans-well assay, respectively. Autophagy and underlying molecular mechanisms were investigated using flow cytometry and western blot analysis. Key findings ATD regulated the activity of PI3K/AKT/mTOR and p38MAPK signalling pathways which contributed to autophagy induction. HuCCT-1 cell growth was inhibited by ATD in a time- and dose-dependent manner. ATD inhibited the migration and invasion of HuCCT1 cells in a concentration-dependent manner. It also induced autophagy in HuCCT1 cells in a time- and dose-dependent manner. The SB202190 (autophagy inducer) and 3-MA (autophagy inhibitor) significantly increased and decreased the rate of ATD-induced autophagy, respectively. The 24 h exposure of ATD inhibited the phosphorylation of phosphatidylinositol-3-kinase (PI3K), protein kinase B (AKT), mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (p38MAPK) and increased Beclin-1 expression and LC3 conversion. It also reduced p-AKT/AKT, p-mTOR/mTOR and p-p38MAPK/p38MAPK. Conclusions ATD inhibits the proliferation and induces CCA cell autophagy via regulating PI3K/AKT/mTOR and p38MAPK signalling pathways.

Automated summary

Atractylodin inhibits proliferation and induces autophagy in cholangiocarcinoma cells by regulating the PI3K/AKT/mTOR and p38MAPK signaling pathways.