Abstract：
BACKGROUND: Prostaglandin D2 (PGD2) has been shown to restrict the occurrence and development of multiple cancers; nevertheless, its underlying molecular mechanism has not been fully elucidated. The present study investigated the effect of PGD2 on the biological function of the enriched gastric cancer stem cells (GCSCs), as well as its underlying molecular mechanism, to provide a theoretical basis and potential therapeutic drugs for gastric cancer (GC) treatment.
METHODS: The plasma PGD2 levels were detected by Enzyme-linked immunosorbent assay (ELISA). Silencing of lipocalin prostaglandin D synthetases (L-PTGDS) and prostaglandin D2 receptor 2 (PTGDR2) was carried out in GCSCs from SGC-7901 and HGC-27 cell lines. Cell Counting Kit-8, transwell, flow cytometry, and western blotting assays were used to determine cell viability, invasion, apoptosis, and stemness of GCSCs. In vivo xenograft models were used to assess tumor growth.
RESULTS: Clinically, it was found that the plasma PGD2 level decreased significantly in patients with GC. PGD2 suppressed viability, invasion, and stemness and increased the apoptosis of GCSCs. Downregulating L-PTGDS and PTGDR2 promoted viability, invasion, and stemness and reduced the apoptosis of GCSCs. Moreover, the inhibition of GCSCs induced by PGD2 was eliminated by downregulating the expression of PTGDR2. The results of in vivo experiments were consistent with those of in vitro experiments.
CONCLUSIONS: Our data suggest that PGD2 may be an important marker and potential therapeutic target in the clinical management of GC. L-PTGDS/PTGDR2 may be one of the critical targets for GC therapy. The PGD2/PTGDR2 signal affects the viability, invasion, apoptosis, and stemness of GCSCs and prevents the progression of GC.
METHODS: The plasma PGD2 levels were detected by Enzyme-linked immunosorbent assay (ELISA). Silencing of lipocalin prostaglandin D synthetases (L-PTGDS) and prostaglandin D2 receptor 2 (PTGDR2) was carried out in GCSCs from SGC-7901 and HGC-27 cell lines. Cell Counting Kit-8, transwell, flow cytometry, and western blotting assays were used to determine cell viability, invasion, apoptosis, and stemness of GCSCs. In vivo xenograft models were used to assess tumor growth.
RESULTS: Clinically, it was found that the plasma PGD2 level decreased significantly in patients with GC. PGD2 suppressed viability, invasion, and stemness and increased the apoptosis of GCSCs. Downregulating L-PTGDS and PTGDR2 promoted viability, invasion, and stemness and reduced the apoptosis of GCSCs. Moreover, the inhibition of GCSCs induced by PGD2 was eliminated by downregulating the expression of PTGDR2. The results of in vivo experiments were consistent with those of in vitro experiments.
CONCLUSIONS: Our data suggest that PGD2 may be an important marker and potential therapeutic target in the clinical management of GC. L-PTGDS/PTGDR2 may be one of the critical targets for GC therapy. The PGD2/PTGDR2 signal affects the viability, invasion, apoptosis, and stemness of GCSCs and prevents the progression of GC.
摘要：
背景：前列腺素D2（PGD2）已被证明可以限制多种癌症的发生和发展；然而，其潜在的分子机制尚未完全阐明。本研究探讨了PGD2对富集胃癌干细胞(GCSCs)生物学功能的影响。以及其潜在的分子机制，为胃癌的治疗提供理论依据和潜在的治疗药物。
方法：采用酶联免疫吸附试验(ELISA)检测血浆PGD2水平。在来自SGC-7901和HGC-27细胞系的GCSC中进行脂质运载蛋白前列腺素D合成酶（L-PTGDS）和前列腺素D2受体2（PTGDR2）的沉默。细胞计数试剂盒-8,transwell,流式细胞术,和蛋白质印迹测定法用于确定细胞活力，入侵,凋亡，和GCSCs的干性。使用体内异种移植模型评估肿瘤生长。
结果：临床，发现GC患者的血浆PGD2水平显着降低。PGD2抑制生存能力，入侵,和干性，增加了GCSCs的凋亡。下调L-PTGDS和PTGDR2促进生存能力，入侵,和干性，减少GCSCs的凋亡。此外，PGD2诱导的GCSC抑制通过下调PTGDR2的表达而消除。体内实验结果与体外实验结果一致。
结论：我们的数据表明PGD2可能是GC临床治疗中的重要标志物和潜在治疗靶点。L-PTGDS/PTGDR2可能是GC治疗的关键靶点之一。PGD2/PTGDR2信号影响生存力，入侵,凋亡，和GCSCs的干性，并阻止GC的进展。
方法：采用酶联免疫吸附试验(ELISA)检测血浆PGD2水平。在来自SGC-7901和HGC-27细胞系的GCSC中进行脂质运载蛋白前列腺素D合成酶（L-PTGDS）和前列腺素D2受体2（PTGDR2）的沉默。细胞计数试剂盒-8,transwell,流式细胞术,和蛋白质印迹测定法用于确定细胞活力，入侵,凋亡，和GCSCs的干性。使用体内异种移植模型评估肿瘤生长。
结果：临床，发现GC患者的血浆PGD2水平显着降低。PGD2抑制生存能力，入侵,和干性，增加了GCSCs的凋亡。下调L-PTGDS和PTGDR2促进生存能力，入侵,和干性，减少GCSCs的凋亡。此外，PGD2诱导的GCSC抑制通过下调PTGDR2的表达而消除。体内实验结果与体外实验结果一致。
结论：我们的数据表明PGD2可能是GC临床治疗中的重要标志物和潜在治疗靶点。L-PTGDS/PTGDR2可能是GC治疗的关键靶点之一。PGD2/PTGDR2信号影响生存力，入侵,凋亡，和GCSCs的干性，并阻止GC的进展。
