The Cyclooxygenase 2 Essay

2602 words - 10 pages

The cyclooxygenase-2 (COX-2) is a key enzyme in the conversion of arachidonic acid to prostaglandins, which promote cell proliferation, angiogenesis and metastasis, and inhibit apoptosis. Unlike COX-1, which is constitutively expressed isoform, COX-2 is an inducible isoform of cyclooxygenase and which may participate in inflammatory responses and contribute to inflammation and cancersthe development of colorectal cancer as well as other human cancers (1). COX-2 is not detectable detected in most normal tissues. However, it but is rapidly induced when stimulated by in response to mitogens, cytokines and tumor promoters, which leads to the leading to increased accumulation of prostanoids in neoplastic and inflamed tissues (2). COX-2 is highly expressed at high levels in intestinal tumors in rodents and humans (1). For example, Mmore than 80% of all colorectal tumors were shown to overexpress COX-2 (3-5). Epidemiologic studies have shown that taking aspirin or other nonsteroidal anti-inflammatory drugs on a regular basis could reduce mortality from colorectal cancer by 40-50% compared with those who not taking these drugs (1). One characteristic shared by all of these drugs is their ability to inhibit COX activity and/or expression (1).

Although COX-2 is expressed in 80-90% of human colon carcinoma specimens, not all colorectal cancer cell lines constitutively expressed COX-2. Constitutive expression of COX-2 was only detected in a relatively small number of established colorectal carcinoma cell lines (6). For example, human colon adenocarcinoma cell lines, HCT116 and SW480, have been described as COX-2 negative, since they did not express COX-2, neither at mRNA nor at protein level (7).

COX-2-derived prostaglandin E2 (PGE2) is the most abundant prostaglandins found in solid malignancies (8). PGE2 is known to stimulate cell migration, proliferation and tumor-associated neovascularization while inhibiting cell death (9). We have examined PGE2 levels in the cell culture medium of two human colorectal cancer cell lines HT29 and Caco-2 cell, and found the PGE2 level was below the detection limit (10). This prompted us to do extensive literature search, and we found that the contradictory results of PGE2 production and COX-2 expression levels in these two colon cancer cell lines were reported in previous studies. Since these two cell lines are extensively used as in vitro colon cancer models, it’s important to correctly characterize COX-2 expression and PGE2 production in these cell lines. This review summarizes the paradoxical observations regarding the levels of COX-2 mRNA and protein and PGE2 production in HT29 and Caco-2 cell lines. The possible reasons of the discrepancies among these finding are also discussed.

2. Inconsistent literature data on COX-2 expression and PGE2 production in HT29 and Caco-2 cell

Literature data show no detectable COX-2 expression and PGE2 production in HT29 and Caco-2 cell lines.
Some literatures show that...

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