Coenzyme Q10 inhibits the activation of pancreatic stellate cells through PI3K/AKT/mTOR signaling pathway

Abstract

Aim: Pancreatic stellate cells (PSCs) have a vital role in pancreatic fibrosis accompanied by pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). Any agents which can affect the activation of PSCs could become potential candidates for treatment strategies in PDAC and CP. Our aim was to explore the effect of Coenzyme Q10 (CoQ10) in the process of PSCs activation. Methods: Isolated PSCs from C57BL/6 mice were treated with various dosages of CoQ10 (1, 10, and 100μM) and different time (24h, 48h, and 72 h). Effect of CoQ10 on autophagy, apoptosis, senescence and oxidative stress, as well as the activation of PSCs were analyzed by immunocytofluorescent staining, quantitative real time RT-PCR, western blotting, SA-β-galactosidase staining, malondialdehyde and reactive oxygen species (ROS) assay. Results: Expression of a-smooth muscle actin, LC3II, Beclin1, Cleaved caspases-3 and Bax levels were significantly reduced in CoQ10 treatment groups. Meanwhile, compared with the control group, significant differences for the expression of desmin, P62, Bcl-2, p-PI3K, p-AKT and p-mTOR levels in CoQ10 treatment groups were found. Moreover, CoQ10 affected the secretion of extracellular matrix components for PSCs. Few SA-β-gal positive cells were found in CoQ10 treated groups. A significant decrease in ROS positive cells and malondialdehyde levels were observed after 72 h exposure to CoQ10. Conclusions: Our finding suggests that CoQ10 inhibits the activation of PSCs by suppressing autophagy through activating the PI3K/AKT/mTOR signaling pathway. CoQ10 may act as a therapeutic agent in PSC-relating pathologies and/or anti-fibrotic approaches.