Expressions Of 5-Lipoxygenase And Cyclooxygenase-2 In Human Colorectal Cancer And The Application Of 5-Lipoxygenase Inhibitor

Objective: To study expressions of 5-Lipoxygenase and Cyclooxygenase-2 in human colorectal cancer, and approach potential mechanism of 5-lox in the promotion and progression of human colorectal cancer, it provides a good theoretical and practical significance For the future diagnosis and treatment of colorectal cancer.Background:Evidence from epidemiological and animal studies suggests that a high-fat consumption is associated with an increased incidence and growth of tumors at several specific organ sites, it has been demonstrated that the metabolism of arachidonic acid, a polyunsaturated fatty acid by either the Cyclooxygenase (cox) pathway or the Lipoxygenase (lox) pathway, generates a host of pro-inflammatory substances called eicosanoids including prostaglandins, thromboxanes, leukotrienes, etc. that act as significance effect of biological in the promotion and progression of many types of human neoplasms. it suggests that the deep investigation ofcyclooxygenase and lipoxygenase possess clinical utility and advanced ,for the future diagnosis and treatment of colorectal cancer provides a good theoretical and practical significance.Part 1 Expressions of 5-Lipoxygenase and Cyclooxygenase-2 in human colorectal tumor and adjacent normal mucosaMethod:1,To investigate the expressions of 5-loxmRNA and cox-2mRNA in paired 39 colorectal cancer samples and their relationship by RT-PCR. 2,The relative quantity of protein 5-lox and cox-2 in colorectal tumor and adjacent normal mucosa samples was determined by western-blot.3,Expressions of 5-Lipoxygenase and Cyclooxygenase-2 in human colorectal cancer samples is related with microvessel density by immunohistochemical staining methods.Result:There were 33 cases of 5-loxmRNA amplified bands of 504bp in39 cases of colorectal cancer tissues, positive expression ratio was 84.6% (33/39); there were 30 cases cox-2mRNA amplified bands of 540bp in 39 cases of colorectal cancer tissues, positive expression ratio was 76.9% (30/39). Expressions of 5-loxmRNA and cox-2mRNA in colorectal cancer tissue were remarkably elevated,and correlated with clinical stage, tumor size,differentiation degree. Expressions of both were not coordinated. Expressions of 5-lox and cox-2 were remarkably elevated in human colorectal tumor tissue in comparison with normal colon mucosa. And the over expression level of 5-lox and cox-2 was positively correlated with microvessel density.Part 2 Expressions of 5-loxmRNA is correlated with expression of bcl-2mRNA and bax mRNA in paired 39 colorectal tumor and adjacent normal mucosa samples and the effect of 5-lox MK886 inhibitor on expression of 5-loxmRNA,bcl-2mRNA and baxmRNAMethod:1,Expressions of 5-loxmRNA,bcl-2mRNA and baxmRNA in paired 39 colorectal tumor and adjacent normal mucosa samples by RT-PCR.2,Expressions of 5-lox mRNA,bcl-2mRNA and baxmRNA compared with before and after MK886 in HT29 colon cancer cell lines.Result:Expressions of 5-loxmRNA,bcl-2mRNA and baxmRNA are separately 33/39, 29/39, 10/39 and 14/39, 10/39, 26/39in paired 39 colorectal tumor and adjacent normal mucosa samples.Expressions of 5-loxmRNA and bcl-2mRNA were more elevated than expression of baxmRNA in human colorectal tumor tissue, Expression of baxmRNA were more higher than expressions of 5-loxmRNA and bcl-2mRNA in human adjacent normal mucosa tissue, Expressions of 5-loxmRNA and bcl-2mRNA were lower by after Mk886 in comparison with befor Mk886 in HT29 colon cancer cell lines. Expressions of baxmRNA were higher by after Mk886 in comparison with before Mk886 in HT29 colon cancer cell lines. Expressions of 5-lox mRNA, bcl-2mRNA are gradually reduced with augmentation of drug concentration, Expression of baxmRNA is gradually increased With augmentation of drug concentration.Conclusion:1,Expressions of 5-loxmRNA and cox-2mRNA were simultaneously up- regulated in human colorectal cancer tissue, Expressions of both were not coordinated.2,Protein expressions of 5-lox and cox-2 were remarkably elevated in human colorectal tumor tissue in comparison with normal colon mucosa.3,The over expressions level of 5-lox and cox-2 was positively correlated with microvessel density.4,5-lox may play a role of promoter in the promotion and development of colorectal cancer by influencing the balance of between cell proliferation and apoptosis.