【摘要】 目的 探讨艾司氯胺酮如何通过SOX9/Wnt/β-catenin信号通路抑制胃癌细胞的恶性进展，并初步探讨可能的潜在机制。方法 采用MTT法、CCK-8、划痕实验、Transwell实验检测和流式细胞术评估细胞活力、增殖、迁移侵袭能力和细胞凋亡。蛋白免疫印迹分析相关蛋白SOX9、β-catenin、磷酸化β-catenin(P-β-catenin)、c-Myc、caspase-3蛋白的表达。结果 艾司氯胺酮能够以剂量依赖性的方式降低AGS细胞的活力(P<0.05)。1、10、100μmol/L能够显著抑制细胞的增殖、迁移和侵袭，并促进细胞凋亡(P<0.05),显著抑制SOX9、P-β-catenin和c-Myc表达(P<0.05),显著促进Caspase-3表达(P<0.05)。与对照组比较，BML-284组细胞增殖率、细胞迁移距离、细胞侵袭率显著增加(P<0.05),凋亡率显著降低(P<0.05),SOX9、P-β-catenin和c-Myc表达水平显著增加(P<0.05),Caspase-3达水平显著降低(P<0.05)。与BML-284组比较，ESK+BML-284组细胞增殖率、细胞迁移距离、细胞侵袭率显著降低(P<0.05),凋亡率显著增加(P<0.05),SOX9、P-β-catenin和c-Myc表达水平显著降低(P<0.05),Caspase-3表达水平显著增加(P<0.05)。与ESK组比较，ESK+BML-284组细胞增殖率、细胞迁移距离、细胞侵袭率显著增加(P<0.05),凋亡率显著降低(P<0.05),SOX9、P-β-catenin和c-Myc表达水平显著增加(P<0.05),Caspase-3达水平显著降低(P<0.05)。结论 艾司氯胺酮能够抑制GC细胞的增殖、迁移和侵袭并诱导细胞凋亡，这可能是通过调节SOX9/Wnt/β-catenin轴以调节下游靶基因c-Myc和Caspase-3的表达来实现的。艾司氯胺酮或可成为治疗GC的辅助药物。更多还原

【Abstract】 Objective To investigate how esketamine(ESK) inhibits the malignant progression of gastric cancer(GC) cells by inhibiting the SOX9/Wnt/β-catenin signaling pathway, and to explore the possible potential mechanisms.Methods Western blot was used to analyze the protein expressions of SOX9,β-catenin, phosphorylated β-catenin(P-β-catenin),c-Myc and caspase-3.Results ESK significantly reduced the viability of AGS cells in a dose-dependent manner(P<0.05). Treatment of ESK at 1μmol/L,10μmol/L,100μmol/L significantly inhibited cell proliferation, migration and invasion, and promoted cell apoptosis(P<0.05),downregulated SOX9,P-β-catenin and c-Myc(P<0.05),and upregulated Caspase-3(P<0.05). Compared with those of blank control, AGS cells induced with BML-284 had significantly higher proliferative rate, migratory distance, and invasive rate, lower apoptotic rate, upregulated SOX9,P-β-catenin and c-Myc, and downregulated Caspase-3(all P<0.05). Compared with those induced with BML-284,AGS cells induced with BML-284 + ESK had significantly lower proliferative rate, migratory distance, and invasive rate, higher apoptotic rate, downregulated SOX9,P-β-catenin and c-Myc, and upregulated Caspase-3(all P<0.05). Compared with those induced with ESK,AGS cells induced with BML-284 + ESK had significantly higher proliferative rate, migratory distance, and invasive rate, lower apoptotic rate, upregulated SOX9,P-β-catenin and c-Myc, and downregulated Caspase-3(all P<0.05).Conclusion ESK can inhibit the proliferation, migration and invasion of GC cells and induce apoptosis by regulating the SOX9/Wnt/β-catenin axis to regulate the expressions of downstream target genes c-Myc and Caspase-3. ESK may be an adjuvant drug for the treatment of GC.更多还原