Octreotide remits endoplasmic reticulum stress to reduce autophagy of intestinal epithelial cell line Caco-2 via upregulation of miR-101.

ABSTRACT

Octreotide (OCT) shows clinical efficacies in the treatment of liver cirrhosis complicated with gastrointestinal hemorrhage. Experiments were designed to investigate its function mechanism associated with endoplasmic reticulum stress (ERS)-induced autophagy and microRNA (miR). Protein associated with ERS and autophagy was detected by western blot. miR-101 was examined by qRT-PCR. Besides, miR-101 or G protein-coupled receptor 78 (GPR78)-silenced Caco-2 cells were established by transfection. Furthermore, western blot was used to determine TGF-beta activated kinase 1 (TAK1), AMPK, mTOR, p70S6K as well as their phosphorylated forms. Lipopolysaccharide (LPS) enforced the expression of GPR78. Besides, LPS triggered the production of Beclin-1 and LC3-II while mitigated the accumulation of p62. Then all these above results were reversed by OCT pretreatment. Moreover, miR-101 expression was downregulated by LPS while upregulated by OCT. Further, miR-101 knockdown strengthened ERS and promoted autophagy. GPR78 silence retarded autophagy process. In the end, OCT mitigated phosphorylation of TAK1, AMPK while enhanced the phosphorylated expression of mTOR and p70S6K in LPS-treated Caco-2 cells. The anti-autophagy property of OCT was mediated by miR-101-induced suppression of GPR78 in LPS-treated Caco-2 cells.