PGD2/PTGDR2 Signaling Affects the Stemness of Gastric Cancer Stem Cells by Regulating Autophagy.

[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 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.