胃癌外泌体上调ABCG8促进肿瘤进展的机制OA

Objective To explore the mechanism by which exosomes derived from gastric cancer cells MGC-803 promote tumor progression through the upregulation of ABCG8 expression.Methods Ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)lipidomics,quantitative real-time PCR(qPCR)and Western blot were used to verify the role of ABCG8 in gastric cancer progression.Exosomes derived from gastric cancer cells were introduced,and a series of in vitro experiments were conducted to evaluate their effect on ABCG8 expression,as well as on cell proliferation,migration,and clonogenic ability in normal gastric mucosal epithelial GES-1 cells.Results UPLC-MS/MS lipidomics analysis revealed significant changes in triacylglycerol(TG)among the differential lipids.qPCR and Western blot analysis showed that the mRNA and protein expression levels of ABCG8 in the GC-Exo-treated group were higher than those in the GES-1 cell group(P<0.05).Colony forma-tion and Transwell migration assays revealed that,compared with the GES-1 cell group,the GC-Exo-treated group exhibited a greater number of colonies(P<0.05)and migrated cells(P<0.05)after 48 h of treatment.CCK-8 as-say results showed that the proliferation rate in the GC-Exo-treated group(50 μg/mL)was higher than that in the GES-1 cell group(P<0.001).Lipidomics analysis revealed that,compared with the GES-1 cell group,TG levels were upregulated in the GC-Exo-treated group,accompanied by decreased levels of phosphatidylcholine(PC)PC(38:2e).Conclusion Exosomes derived from gastric cancer cells MGC-803 may promote tumor progression by upregulating ABCG8 expression to mediate cholesterol efflux,thereby triggering pro-carcinogenic lipid metabolic reprogramming in normal gastric mucosal epithelial cells.