Division of Gastroenterology and Hepatology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
Department of Anesthesiology, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
Int J Mol Med. 2017 Aug;40(2):512-522. doi: 10.3892/ijmm.2017.3011. Epub 2017 Jun 2.
The conversion of arachidonic acid into prostaglandins by cyclooxygenase (COX)-2 contributes to the biological properties of malignant tumours. During the initiation and development of various tumours, the Notch family plays a key role. However, the association between COX‑2 and the Notch family in gastric cancer (GC) remains unclear. The present study aimed to clarify the mechanisms through which COX‑2 participates in the pathogenesis of GC. Quantitative PCR and western blot analysis were used to detect the expression of Notch family members and COX‑2 in human GC and paracancerous tissues, GES‑1 cells and GC cell lines (AGS, SGC‑7901, BGC‑823, and MGC‑803) treated with or without celecoxib, prostaglandin E2 and small interfering RNA (siRNA). A CCK‑8 assay was performed to detect the proliferation of GC cells transfected with siRNA against COX‑2 (si‑COX‑2). A high mRNA expression of Notch1 and a decreased expression of Notch-1 intracellular active domain (N1IC) in GC were found to be related to the depth of invasion and TNM staging. The mRNA levels of Notch2, Notch3, Jagged1 and N2IC were found to be high in GC. A High expression of COX‑2 was associated with poorly differentiated and deeply invasive GC. COX‑2 and Notch1 exhibited an inverse expression pattern in the GES‑1 cells and different GC cell lines; the inhibition of COX‑2 increased Notch1 expression and activated the GC cells, whereas Notch1 downregulation had the opposite effect. Notch1 exhibited varying effects on Snail in the GC cell lines. The downregulation of COX‑2 expression significantly inhibited the proliferation of GC cells. On the whole, the expression of Notch signalling molecules differed in GC. COX‑2 inversely regulated Notch1 in GC and partially depended on the Notch1 signalling pathway in altering the expression of Snail.
环氧化酶-2（COX-2）将花生四烯酸转化为前列腺素，这有助于恶性肿瘤的生物学特性。在各种肿瘤的发生和发展过程中，Notch 家族发挥着关键作用。然而，COX-2 与胃癌（GC）中的 Notch 家族之间的关联尚不清楚。本研究旨在阐明 COX-2 参与 GC 发病机制的机制。采用定量 PCR 和 Western blot 分析检测人 GC 和癌旁组织、GES-1 细胞和 GC 细胞系（AGS、SGC-7901、BGC-823 和 MGC-803）中 Notch 家族成员和 COX-2 的表达，这些细胞系经塞来昔布、前列腺素 E2 和小干扰 RNA（siRNA）处理或未处理。通过 CCK-8 测定法检测转染针对 COX-2 的 siRNA（si-COX-2）的 GC 细胞的增殖。发现 GC 中 Notch1 的高 mRNA 表达和 Notch-1 细胞内活性结构域（N1IC）的表达降低与浸润深度和 TNM 分期有关。Notch2、Notch3、Jagged1 和 N2IC 的 mRNA 水平在 GC 中较高。COX-2 的高表达与 GC 的低分化和浸润深度有关。COX-2 和 Notch1 在 GES-1 细胞和不同 GC 细胞系中呈相反的表达模式；COX-2 的抑制增加了 Notch1 的表达并激活了 GC 细胞，而 Notch1 的下调则产生相反的效果。Notch1 在 GC 细胞系中对 Snail 表现出不同的作用。下调 COX-2 的表达可显著抑制 GC 细胞的增殖。总的来说，GC 中 Notch 信号分子的表达不同。COX-2 以 GC 中 Notch1 的相反方式调节，部分依赖于 Notch1 信号通路来改变 Snail 的表达。
