Helicobacter pylori (H. pylori) infection promotes the metastasis of gastric carcinoma cells by modulating signal transduction pathways that regulate cell proliferation, motility, and invasion. Astaxanthin (ASTX), a xanthophyll carotenoid, is known to inhibit cancer cell migration and invasion, however the mechanism of action of ASTX in H. pylori-infected gastric epithelial cells is not well understood. To gain insight into this process, we carried out a comparative RNA sequencing (RNA-Seq) analysis of human gastric cancer AGS (adenocarcinoma gastric) cells as a function of H. pylori infection and ASTX administration. The results were used to identify genes that are difierently expressed in response to H. pylori and ASTX. Gene ontology (GO) analysis identified difierentially expressed genes (DEGs) to be associated with cell cytoskeleton remodeling, motility, and/or migration. Among the 20 genes identified, those encoding c-MET, PI3KC2, PLC1, Cdc42, and ROCK1 were selected for verification by real-time PCR analysis. The verified genes were mapped, using signaling networks contained in the KEGG database, to create a signaling pathway through which ASTX might mitigate the e_ects of H. pylori-infection. We propose that H. pylori-induced upregulation of the upstream regulator c-MET, and hence, its downstream targets Cdc42 and ROCK1, is suppressed by ASTX. ASTX is also suggested to counteract H. pylori-induced activation of PI3K and PLC. In conclusion, ASTX can suppress H. pylori-induced gastric cancer progression by inhibiting cytoskeleton reorganization and reducing cell motility through downregulation of c-MET, EGFR, PI3KC2, PLC1, Cdc42, and ROCK1.
|Publication status||Published - 2020 Jul|
Bibliographical noteFunding Information:
Funding: This study was supported by a grant from the National Research Foundation (NRF) of Korea, which is funded by the Korean Government (NRF-2018R1A2B2005575).
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All Science Journal Classification (ASJC) codes
- Drug Discovery