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目的 探讨胃癌细胞MGC-803来源的外泌体通过上调ABCG8表达促进肿瘤发展的机制。方法 采用超高效液相色谱-串联质谱（UPLC-MS/MS）脂质组学技术，Western blot、实时定量PCR(qPCR)等方法，验证ABCG8在胃癌进程中的作用。引入胃癌细胞来源的外泌体（GC-Exo），开展一系列体外实验，评估其对胃正常黏膜上皮细胞GES-1中ABCG8表达及细胞增殖、迁移和克隆形成能力的影响。结果 UPLC-MS/MS脂质组学分析显示，细胞三酰甘油（TG）在差异脂质中呈显著变化。qPCR和Western blot检测显示，与GES-1细胞组相比，GC-Exo处理组中ABCG8的mRNA和蛋白表达水平高于GES-1细胞组（P<0.05）；克隆形成实验及迁移实验结果显示，与GES-1细胞组比较，GC-Exo处理组克隆形成数增多（P<0.05），迁移细胞数增多（P<0.05）；细胞计数试剂盒-8(CCK-8)实验结果显示，GC-Exo处理组细胞增殖速率高于GES-1细胞组（P<0.001）。脂质组学分析显示，与GES-1细胞组相比，GC-Exo处理组中的TG上调，伴随磷脂酰胆碱（PC）中PC(38:2e)降低。结论 胃癌细胞MGC-803来源的外泌体可能通过上调ABCG8表达介导胆固醇外排，从而触发GES-1细胞的促癌脂质代谢特征改变，促进肿瘤进展。
Abstract：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.
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基本信息:
DOI：10.19405/j.cnki.issn1000-1492.2026.09.005
中图分类号:R735.2
引用信息:
[1]邵明凯,陈文通,王丽,等.胃癌外泌体上调ABCG8促进肿瘤进展的机制[J].安徽医科大学学报,2026(09):1541-1547.DOI:10.19405/j.cnki.issn1000-1492.2026.09.005.
基金信息:
安徽省高等学校科学研究项目(编号:2023AH050578); 安徽省级研究生学术创新创业实践项目(编号:2024cxcysj066)
2026-08-13
2026-08-13
2026-08-13