COX-2 regulates Snail expression in gastric cancer via the Notch1 signaling pathway

  • Authors:
    • Yuwei Ye
    • Min Liu
    • Hao Yuan
    • Shupeng Ning
    • Yuping Wang
    • Zhaofeng Chen
    • Rui Ji
    • Qinghong Guo
    • Qiang Li
    • Yongning Zhou
  • View Affiliations

  • Published online on: June 2, 2017     https://doi.org/10.3892/ijmm.2017.3011
  • Pages: 512-522
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Abstract

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.
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August-2017
Volume 40 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Ye Y, Liu M, Yuan H, Ning S, Wang Y, Chen Z, Ji R, Guo Q, Li Q, Zhou Y, Zhou Y, et al: COX-2 regulates Snail expression in gastric cancer via the Notch1 signaling pathway. Int J Mol Med 40: 512-522, 2017
APA
Ye, Y., Liu, M., Yuan, H., Ning, S., Wang, Y., Chen, Z. ... Zhou, Y. (2017). COX-2 regulates Snail expression in gastric cancer via the Notch1 signaling pathway. International Journal of Molecular Medicine, 40, 512-522. https://doi.org/10.3892/ijmm.2017.3011
MLA
Ye, Y., Liu, M., Yuan, H., Ning, S., Wang, Y., Chen, Z., Ji, R., Guo, Q., Li, Q., Zhou, Y."COX-2 regulates Snail expression in gastric cancer via the Notch1 signaling pathway". International Journal of Molecular Medicine 40.2 (2017): 512-522.
Chicago
Ye, Y., Liu, M., Yuan, H., Ning, S., Wang, Y., Chen, Z., Ji, R., Guo, Q., Li, Q., Zhou, Y."COX-2 regulates Snail expression in gastric cancer via the Notch1 signaling pathway". International Journal of Molecular Medicine 40, no. 2 (2017): 512-522. https://doi.org/10.3892/ijmm.2017.3011