Enhancement of colon carcinogenesis by prostaglandin E2 administration

Abstract

Although an accumulating body of evidence indicates that levels of prostaglandin E 2 (PGE 2 ) in human and rodent colon cancers are higher than those in surrounding normal tissues, the precise contribution of PGE 2 to the process of colon cancer development has still been unclear. Therefore, we designed a study using a well-established azoxymethane (AOM)-induced colon carcinogenesis in male F344 rat model to investigate whether administration of exogenous PGE 2 has a real impact on colon carcinogenesis. Intraperitoneal PGE 2 injections (7.7 mg) once a week for 25 weeks significantly increased the AOM-induced colon tumor incidence (percent rats with tumors, 92 versus 53%, P 5 0.05), especially adenocarcinomas (92 versus 47%, P 5 0.05), and multiplicity (number of tumors per rat, 2.8 versus 1.0, P 5 0.05). PGE 2 treatment significantly increased 5-bromo-2 H -deoxyuridine (BrdUrd) labeling index (11.8 versus 9.7%, P 5 0.05) and reduced apoptotic index (0.34 versus 0.53%, P 5 0.05) in colon cancers induced by AOM. PGE 2 exhibits its physiological functions through binding to E-prostanoid (EP) membrane receptors EP 1À4 . All four types of EP receptors were detected in AOM-induced colon cancers using reverse transcription± polymerase chain reaction (RT±PCR). Our results provide evidence that PGE 2 enhances colon carcinogenesis through induction of cell proliferation and reduction of apoptosis.

Intratumoral forkhead box P3‐positive regulatory T cells predict poor survival in cyclooxygenase‐2–positive uveal melanoma

“…[21][22][23] The overexpression of COX-2 has been linked to several cancer hallmarks, including the inhibition of apoptotic signaling, progression of the cell cycle, and sustained angiogenesis. [18][19][20] Because COX-2 is a PG synthase, its overexpression obviously results in increased PGE 2 levels. Multiple immunomodulatory effects of PGE 2 have been demonstrated and suggest that it makes a strong contribution to tumor evasion from the immune system.…”

“…Furthermore, the COX-2/PGE 2 pathway is attributed to immune-modulating effects that strongly contribute to an immunosuppressive microenvironment, and 1 of those effects is the association with Tregs, as described previously. [18][19][20][21] Recent reports have demonstrated the expression of COX-2 in UM and its impact on the course of the disease. 22,23 The current study was designed to explore the relation between COX-2 expression and the prevalence of FOXP3-positive Tregs in terms of an immunomodulatory mechanism potentially important for the course of the disease.…”

Expression of Cyclooxygenase-2 (COX-2) in Colorectal Adenocarcinoma: an Immunohistochemical and Histopathological Study

“…COX -1 and COX-2 catalyze the first stage in the oxidation of arachidonic acid to prostaglandin (Karahan et al, 2007). Prostaglandin E(2) increases colon carcinogenesis through induction of cell proliferation and reduction of apoptosis (Kawamori et al, 2003). The majority of the colorectal cancers are derived from adenomas (Wu et al, 2003).…”

The EP4 receptor antagonist, L-161,982, blocks prostaglandin E2-induced signal transduction and cell proliferation in HCA-7 colon cancer cells

“…Elevated levels of PGE 2 as a result of COX-2 overexpression were observed in human colorectal tumors as well as in carcinogen-treated rats [4][5][6]. PGE 2 treatment was shown to enhance incidence of colonic tumors in AOM-treated rats and attenuates non-steroidal anti-inflammatory drug (NSAID)-induced tumor regression in Apc Min/+ mice by increasing intestinal epithelial cell proliferation and reduction of apoptosis [7][8][9]. In addition, PGE 2 can increase cell survival, invasion, and migration of human colon cancer cells [10][11][12].…”