Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China (mainland).
Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China (mainland).
Med Sci Monit. 2019 Mar 4;25:1663-1670. doi: 10.12659/MSM.912338.
BACKGROUND As a member of the zinc-finger E-box binding protein (ZEB) family, ZEB1 can modulate onset and progression of various tumors, but its regulatory effect or mechanism in GC has not been defined. MATERIAL AND METHODS GC tumor tissues and adjacent tissues were collected from GC patients across different TNM stages. Real-time PCR was used to measure ZEB1 expression to analyze its correlation with pathological features of tumors. Cultured GC cell lines SGC-7901 and MGC-803 were randomly assigned into control group, scramble group, and ZEB1 siRNA group. Real-time PCR was employed to analyze ZEB1 expression, and MTT approach was used to measure cell proliferation. Cell apoptosis was evaluated by flow cytometry. Wound healing assay was used to detect its effect on cell migration. Expression of E-cadherin and Vimentin involved in epithelial-to-mesenchymal transition (EMT) was measured by Western blot analysis, along with Wnt5a proteins. RESULTS GC tissues had upregulation of ZEB1 (P<0.05 compared to adjacent tissues), whose expression level was correlated with differentiation grade, lymph node metastasis, and tumor pathological stage (P<0.05). Transfection of ZEB1 siRNA into SGC-7901 or MGC-803 cells can suppress ZEB1 expression, inhibit tumor cell proliferation, enhance apoptosis, and inhibit cell migration. Transfected GC cells had higher E-cadherin expression and decreased Vimentin expression or Wnt5a expression (P<0.05 compared to the control group). CONCLUSIONS ZEB1 expression is increased in GC tumor tissues and is associated with pathological features. The downregulation of ZEB1 can facilitate cell apoptosis via mediating Wnt5a, further suppressing GC cell proliferation and migration, and reducing EMT occurrence.
作为锌指 E 盒结合蛋白（ZEB）家族的一员，ZEB1 可以调节各种肿瘤的发生和进展，但它在 GC 中的调节作用或机制尚未确定。
收集不同 TNM 分期的 GC 患者的 GC 肿瘤组织和相邻组织。实时 PCR 用于测量 ZEB1 表达，分析其与肿瘤病理特征的相关性。将培养的 GC 细胞系 SGC-7901 和 MGC-803 随机分为对照组、乱序组和 ZEB1 siRNA 组。实时 PCR 用于分析 ZEB1 表达，MTT 法用于测量细胞增殖。流式细胞术评估细胞凋亡。划痕愈合试验用于检测细胞迁移的影响。Western blot 分析测量上皮间质转化（EMT）相关的 E-钙粘蛋白和波形蛋白的表达，以及 Wnt5a 蛋白。
GC 组织中 ZEB1 上调（与相邻组织相比，P<0.05），其表达水平与分化程度、淋巴结转移和肿瘤病理分期相关（P<0.05）。将 ZEB1 siRNA 转染到 SGC-7901 或 MGC-803 细胞中可以抑制 ZEB1 表达，抑制肿瘤细胞增殖，增强细胞凋亡，抑制细胞迁移。转染 GC 细胞后 E-钙粘蛋白表达升高，波形蛋白或 Wnt5a 表达降低（与对照组相比，P<0.05）。
ZEB1 在 GC 肿瘤组织中表达增加，与病理特征相关。下调 ZEB1 通过介导 Wnt5a 促进细胞凋亡，进一步抑制 GC 细胞增殖和迁移，减少 EMT 发生。
