Octreotide Alleviates Autophagy by Up-Regulation of MicroRNA-101 in Intestinal Epithelial Cell Line Caco-2

Abstract

Background: Intestinal mucositis is a common side-effect after anti-cancer therapy, which may greatly restrict the therapeutic effects. We aimed to explore the functional role of octreotide (OCT) in lipopolysaccharide (LPS)-induced autophagy of human intestinal epithelial cells as well as the underlying mechanisms. Methods: Cell viability and expression of proteins related to autophagy, AMPK and the mTOR pathway in LPS-treated Caco-2 cells were determined by CCK-8 assay and Western blot analysis, respectively. Effects of OCT on LPS-induced alterations as well as miR-101 expression were measured. Then, miR-101 was aberrantly expressed, and whether OCT alleviated LPS-induced autophagy through miR-101 was tested. Next, whether TGF-β-activated kinase 1 (TAK1) was involved in the regulation of miR-101 in LPS-induced autophagy was studied. Effects of OCT on monolayer permeability and tight junction level were analyzed via measuring transepithelial electrical resistance (TEER) and expression of tight junction proteins. Results: LPS reduced cell viability and increased autophagy through activating AMPK and inhibiting the mTOR pathway in Caco-2 cells. OCT alleviated LPS-induced alterations and repressed degradation of autophagosome. Then, we found that OCT affected autophagy through up-regulating miR-101 in LPS-treated cells. Moreover, miR-101-induced inactivation of AMPK and activation of the mTOR pathway in LPS-treated cells were reversed by inhibition of TAK1 phosphorylation. Finally, we found miR-101 was up-regulated in differentiated cells, and OCT protected the monolayer permeability and tight junction level. Conclusion: OCT repressed autophagy through miR-101-mediated inactivation of TAK1, along with inactivation of AMPK and activation of the mTOR pathway in LPS-treated Caco-2 cells.