Ann Coloproctol.  2022 Apr;38(2):153-159. 10.3393/ac.2021.00374.0053.

Upregulation of prostaglandin E₂ by inducible microsomal prostaglandin E synthase-1 in colon cancer

• Kim YH
• Kim KJ

• KMID: 2528186
• DOI: http://doi.org/10.3393/ac.2021.00374.0053

Abstract

Purpose
Prostaglandin E₂ (PGE₂) is known to promote carcinogenesis and cancer progression in colon cancer. Enzymes involved in the metabolism of PGE₂ include cyclooxygenase (COX)-2, microsomal prostaglandin E synthase-1 (mPGES-1), and 15-prostaglandin dehydrogenase (15-PGDH). The current study aims to determine how PGE₂ is expressed by examining patients with colorectal cancer and evaluating colon cancer cells to gain insight into changes in relevant enzymes upon induction of PGE₂.
Methods
The concentration of PGE₂ was measured in tumor tissues and adjacent normal mucosal tissues of 26 patients with colon cancer. The expression of COX-1, COX-2, mPGES-1, and 15-PGDH proteins was measured. The concentration of PGE₂ in FET colon cancer cells was measured both in the initial status and after stimulation by tumor necrosis factor (TNF)-α. The expression levels of PGE₂-related enzymes were measured as well.
Results
There was no significant difference in the average concentration of PGE₂, which was measured at 453.1 pg/mL in cancer tissues and 401.2 pg/mL in normal mucosa. Among PGE₂-related enzymes, 15-PGDH was expressed at a lower level in tumor cells than in normal mucosa. In colon cancer cells, PGE₂ was found to be upregulated upon stimulation by TNF-α, which led to strong induction of mPGES-1 without any change in the expression of COX-2 among the PGE₂-related enzymes.
Conclusion
These results demonstrated that PGE₂ can be induced by stimuli such as TNF-α, and suggest that activation of mPGES-1 is more closely related than that of COX-2 in the induction of PGE₂ on colon cancer.

Keyword

Colonic neoplasms; Dinoprostone; Prostaglandin-E synthases; Cyclooxygenase 2; 15-Hydroxyprostaglandin dehydrogenase