Department of Gastrointestinal-pancreatic Surgery, Shanxi Province People's Hospital, Taiyuan, China.
Department of Gastrointestinal-pancreatic Surgery, Shanxi Province People's Hospital, Taiyuan, China.
Cytokine. 2022 Nov;159:156013. doi: 10.1016/j.cyto.2022.156013. Epub 2022 Sep 3.
Gastric cancer (GC) is one of the most common malignant tumours and has a high fatality rate worldwide. This study investigated the role of the Notch-1 signalling pathway in the pathogenesis and progression of GC.
A total of 64 patients with GC were included in this study. Immunohistochemistry staining was used to detect Notch-1 expression in tumour tissues and adjacent non-tumour tissues, and Notch-1 knockdown in GC cells was identified using short hairpin RNA. A cell scratch assay, transwell assay and flow cytometry analysis were used to analyse the effect of Notch-1 knockdown on cell proliferation, migration and cell cycle distribution. The expression of Notch-1, PTEN, Akt, ERK1/2, E-cadherin and other proteins was detected using Western blotting.
The expression level of Notch-1 in GC tissues was higher than that in adjacent non-tumour tissues (P < 0.05). High levels of Notch-1 were also found to be associated with sex (male) and lymph node metastasis (P < 0.05). Notch-1 knockdown in the AGS and BGC-823 GC cell lines inhibited the migration and proliferation of GC cells, and Notch-1 knockdown arrested the cell cycle in the G0/G1 phase. PTEN protein expression was elevated in the presence of Notch-1 knockdown, resulting in the inhibition of phosphorylated Akt protein expression. In addition, phosphorylated ERK protein levels decreased in the presence of Notch-1 knockdown. Further inhibition of ERK1/2 signalling by the MEK1/2 inhibitor U0126 decreased the proliferation of AGS cells. The results of in vivo experiments with xenotransplantation in nude mice are consistent with these results.
Notch-1 plays a key role in the development of GC and was found to promote the lymph node metastasis of GC. Notch-1 knockdown can effectively attenuate the progression of GC cells, which may function in part through the Notch-1-PTEN-ERK1/2 signalling axis.
胃癌（GC）是最常见的恶性肿瘤之一，在全球范围内具有较高的死亡率。本研究探讨了 Notch-1 信号通路在 GC 发病机制和进展中的作用。
本研究纳入了 64 例 GC 患者。采用免疫组织化学染色检测肿瘤组织和相邻非肿瘤组织中 Notch-1 的表达，并用短发夹 RNA 敲低 GC 细胞中的 Notch-1。通过细胞划痕实验、Transwell 实验和流式细胞术分析，分析 Notch-1 敲低对细胞增殖、迁移和细胞周期分布的影响。采用 Western blot 检测 Notch-1、PTEN、Akt、ERK1/2、E-cadherin 等蛋白的表达。
GC 组织中 Notch-1 的表达水平高于相邻非肿瘤组织（P<0.05）。高水平的 Notch-1 还与性别（男性）和淋巴结转移有关（P<0.05）。AGS 和 BGC-823 GC 细胞系中 Notch-1 的敲低抑制了 GC 细胞的迁移和增殖，并且 Notch-1 的敲低使细胞周期停滞在 G0/G1 期。Notch-1 敲低时，PTEN 蛋白表达升高，导致磷酸化 Akt 蛋白表达抑制。此外，Notch-1 敲低时磷酸化 ERK 蛋白水平降低。MEK1/2 抑制剂 U0126 进一步抑制 ERK1/2 信号通路可降低 AGS 细胞的增殖。裸鼠异种移植体内实验的结果与这些结果一致。
Notch-1 在 GC 的发生发展中起关键作用，并促进 GC 的淋巴结转移。Notch-1 敲低可有效抑制 GC 细胞的进展，其部分作用机制可能是通过 Notch-1-PTEN-ERK1/2 信号通路。
