PMID- 28586004 OWN - NLM STAT- MEDLINE DCOM- 20180530 LR - 20220330 IS - 1791-244X (Electronic) IS - 1107-3756 (Linking) VI - 40 IP - 2 DP - 2017 Aug TI - COX-2 regulates Snail expression in gastric cancer via the Notch1 signaling pathway. PG - 512-522 LID - 10.3892/ijmm.2017.3011 [doi] AB - 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. FAU - Ye, Yuwei AU - Ye Y AD - Division of Gastroenterology and Hepatology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China. FAU - Liu, Min AU - Liu M AD - Division of Gastroenterology and Hepatology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China. FAU - Yuan, Hao AU - Yuan H AD - Division of Gastroenterology and Hepatology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China. FAU - Ning, Shupeng AU - Ning S AD - Department of Anesthesiology, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China. FAU - Wang, Yuping AU - Wang Y AD - Division of Gastroenterology and Hepatology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China. FAU - Chen, Zhaofeng AU - Chen Z AD - Division of Gastroenterology and Hepatology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China. FAU - Ji, Rui AU - Ji R AD - Division of Gastroenterology and Hepatology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China. FAU - Guo, Qinghong AU - Guo Q AD - Division of Gastroenterology and Hepatology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China. FAU - Li, Qiang AU - Li Q AD - Division of Gastroenterology and Hepatology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China. FAU - Zhou, Yongning AU - Zhou Y AD - Division of Gastroenterology and Hepatology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China. LA - eng PT - Journal Article DEP - 20170602 PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (NOTCH1 protein, human) RN - 0 (Receptor, Notch1) RN - 0 (Snail Family Transcription Factors) RN - EC 1.14.99.1 (Cyclooxygenase 2) SB - IM MH - Cell Line, Tumor MH - Cell Proliferation MH - Cyclooxygenase 2/*genetics MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - Receptor, Notch1/*genetics MH - Signal Transduction MH - Snail Family Transcription Factors/*genetics MH - Stomach/pathology MH - Stomach Neoplasms/*genetics/pathology EDAT- 2017/06/07 06:00 MHDA- 2018/05/31 06:00 CRDT- 2017/06/07 06:00 PHST- 2016/11/01 00:00 [received] PHST- 2017/05/19 00:00 [accepted] PHST- 2017/06/07 06:00 [pubmed] PHST- 2018/05/31 06:00 [medline] PHST- 2017/06/07 06:00 [entrez] AID - 10.3892/ijmm.2017.3011 [doi] PST - ppublish SO - Int J Mol Med. 2017 Aug;40(2):512-522. doi: 10.3892/ijmm.2017.3011. Epub 2017 Jun 2.