Effects of FTY720 activation of PI3K signaling pathway to induce autophagy on proliferation and migration of gastric cancer cells

Abstract

Abstract Background Fingolimod (FTY720), a synthetic analogue of myriocon, has been the subject of numerous studies investigating its antitumor activity. Autophagy, a distinctive cellular process in eukaryotic cells, has been extensively explored in cancer metastasis research.The mechanisms by which FTY720 regulates autophagy in gastric cancer are still not clear.Therefore, exploring the relationship between FTY720 and autophagy regulation will help provide a new perspective for GC treatment. Methods We are using gene database analysis to investigate the impact of FTY720 on tumor progression. We aim to elucidate the effects of FTY720 on the biological behavior of gastric cancer cells SGC-7901 and HGC-27 in vitro, particularly focusing on the regulation of autophagy, as well as its influence on tumor growth in vivo. We will integrate histological and molecular methods to assess the biological behavior and explore the molecular mechanisms both in vitro and in vivo. Results Based on the database used in this investigation, it was discovered that FTY720 might inhibit the proliferation of cancer cells via inducing autophagy.FTY720 functions as a regulatory factor to promote autophagy expression, prevent GC cell proliferation, migration, and invasion in culture, and slow the formation of tumors in vivo.Experiments using the autophagy inhibitor (HCQ) revealed that FTY720's regulatory inhibition was dramatically reduced.Additionally, we showed that FTY720 significantly boosted PI3K phosphorylation levels although its total protein levels in GC cell lines did not alter appreciably. Conclusion In conclusion, our study demonstrated that FTY720 activates the PI3K pathway to cause autophagy, limit GC cell migration and invasion, and induce autophagy. It also suggested that FTY720 signaling molecules may be used as prospective GC therapeutic targets.