The importance of arachidonic acid and linoleic acid metabolism is supported by animal and human epidemiology studies that indicate that aspirin and other NSAIDs reduce the incidence and mortality of colon cancer. These drugs also induce regression of rectal polyps in patients with familial polyposis. Experimental studies with rodents indicate that NSAIDs reduce both the size and number of colon tumors induced by carcinogens. Recent studies reported that Cox-2 is significantly expressed in colon cancer and other cancers. Some data suggest effects of prostaglandins are via modulation of apoptosis and angiogenesis. We are examining arachidonic and linoleic acid metabolism, and the expression of Cox-1 and -2, lipoxygenases, human cell lines. Using CaCo-2 cells as a model for human colorectal epithelium, we have studied the expression of Cox-2, -1 and 15-LO during apoptosis and differentiation. Apoptosis and differentiation is accompanied by a decrease in the expression of Cox-2 and an increase in expression of 15-LO. Evidence suggests that the expression of 15-LO is part of the apoptosis and cell differentiation process. We have also examined the expression of 15-LO in human colorectal tumors and adjacent normal tissue. 15-LO is expressed in colorectal epithelial cells and a higher expression was observed in the tumor samples. Further studies are planned to investigate how the expression of Cox-2 and 15-LO modulates the development of colorectal tumors.

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