Although
colon cancer is one of the most important triggers of
cancer related mortality, a few therapeutic options exist for this disease, including
combination chemotherapy, anti-EGFR and anti-angiogenic agents. However, none of these
therapeutics are fully effective for complete remission, and this issue needs further investigations, particularly in the patients with advanced disease. It has been shown that colon
carcinogenesis process is associated with upregulation of
prostaglandin (PG) levels. Moreover, conversion of pre-malignant cells to malignant was also related with increased generation of PGs in susceptible subjects. Among the
prostanoids,
PGE2 is the most important produced member which generated in high levels by colon
tumor cells. Generation of
PGE2 by action of
cyclooxygenase (COX)-2 can promote growth and development, resistance to apoptosis, proliferation, invasion and
metastasis, angiogenesis and drug resistance in
colon cancer. Increased levels of
PGE2 and COX-2 in
colon cancer is reported by various investigators which was associated with
disease progression. It is suggested that there is a positive feedback loop between COX-2 and
PGE2, in which function of COX-2 induces generation of
PGE2, and upregulation of
PGE2 increases the expression of COX-2 in
colon cancer. Although an existence of this feedback loop is well-documented, its precise mechanism, signaling pathways, and the particular E-type
prostanoid (EP) receptor mediating this feedback are elusive. Therefore, it seems that targeting COX-2/
PGE2/EP receptors may be supposed as a potent therapeutic strategy for treatment of
colon cancer. In this review, we try to clarify the role of
PGE2 in
cancer progression and its targeting for treatment of
colon cancer.