PGD2/PTGDR2信号通路通过调节自噬影响胃癌干细胞的干性。
PGD2/PTGDR2 Signaling Affects the Stemness of Gastric Cancer Stem Cells by Regulating Autophagy.
作者信息
Wang Feifan, Tian Hengjin, Gao Peiyao, Cha Zhanshan, Zhang Qiang
机构信息
Department of Blood Transfusion, The First Affiliated Hospital of Naval Medical University, Shanghai, China.
Department of Clinical Laboratory, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China.
出版信息
Comb Chem High Throughput Screen. 2025 Jan 27. doi: 10.2174/0113862073372570250123091700.
BACKGROUND
Prostaglandin D2 (PGD2) can inhibit the development of gastric cancer (GC); however, its role in the autophagic death of GC stem cells (GCSCs) remains elusive. Therefore, this study aims to evaluate the mechanisms by which PGD2 regulates the stemness in GCSCs.
METHODS
In this study, HGC27-derived GCSCs were employed to knock down PGD2 receptor 2 (PTGDR2). Subsequently, cell stemness and autophagic activity in these GCSCs were assessed via sphere-forming capacity, transmission electron microscopy, and western blot analyses.
RESULTS
The results revealed that PGD2 suppressed the stemness of GCSCs and induced GCSCs autophagy, whereas the downregulation of PTGDR2 had the opposite effect. Furthermore, PGD2 was also found to inhibit the expression of stemness-associated proteins CD44 and OCT4, which were blocked by 3-MA and enhanced by RAPA. Moreover, the shPTGDR2 + PGD2 group indicated higher stemness than the PGD2 group, with 3-MA enhancing this effect and RAPA reducing this change.
CONCLUSION
In summary, this study indicated that PGD2/PTGDR2 signaling affects stemness and autophagy in GCSCs. The results suggest that PGD2/PTGDR2 signaling may affect the stemness of GCSCs by regulating autophagy.
背景
前列腺素D2（PGD2）可抑制胃癌（GC）的发展；然而，其在胃癌干细胞（GCSCs）自噬性死亡中的作用仍不清楚。因此，本研究旨在评估PGD2调节GCSCs干性的机制。
方法
在本研究中，采用源自HGC27的GCSCs敲低PGD2受体2（PTGDR2）。随后，通过成球能力、透射电子显微镜和蛋白质免疫印迹分析评估这些GCSCs中的细胞干性和自噬活性。
结果
结果显示，PGD2抑制GCSCs的干性并诱导GCSCs自噬，而PTGDR2的下调则产生相反的效果。此外，还发现PGD2抑制干性相关蛋白CD44和OCT4的表达，3-MA可阻断这种抑制作用，雷帕霉素（RAPA）则可增强这种抑制作用。此外，shPTGDR2 + PGD2组的干性高于PGD2组，3-MA增强了这种效果，而RAPA则减少了这种变化。
结论
总之，本研究表明PGD2/PTGDR2信号传导影响GCSCs的干性和自噬。结果表明，PGD2/PTGDR2信号传导可能通过调节自噬来影响GCSCs的干性。
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