ROLE OF LIPIDS IN COLON CANCER

工作总结：花生四烯酸和亚油酸的重要性 动物和人类流行病学研究支持代谢， 表明阿司匹林和其他非甾体抗炎药降低了发病率和死亡率 结肠癌这些药物也可诱导直肠息肉消退， 家族性息肉病患者。 啮齿动物实验研究 表明非甾体类抗炎药可以减少结肠肿瘤的大小和数量 由致癌物质引起的。 最近的研究报道，PGHS-2是 与邻近正常组织相比，在结肠肿瘤中显著表达 组织中的APC基因突变直接与 PGHS-2在肿瘤中的表达。因此，苏格兰人扮演着一个重要的角色， 在结肠癌的发展和进展中的作用，但其机制 还不清楚。一些数据表明，芦荟素的作用是通过 细胞凋亡的调节。 我们正在检查花生四烯酸和亚油酸 代谢以及PGHS-1和PGHS-2、脂氧合酶和cPLA 2的表达 在人类细胞系中。 我们观察到，在SW-480和其他人类结肠细胞中， 丁酸盐诱导的分化导致了 PGHS-1和脂氧合酶的结合。 PGHS-2在这些癌症中表达高 细胞，但表达不改变丁酸盐的降解。 丁酸 也诱导细胞凋亡，但PGHS抑制剂的加入并没有改变 这些细胞的凋亡。 我们也用老鼠的肠细胞 高表达PGHS-2并用作结肠癌模型的细胞系。 这些研究将进一步确定NSAID的潜在用途， 化疗药物，并希望更好地定义脂质的作用， 结肠癌

Summary of Work: 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 PGHS-2 is significantly expressed in colon tumors compared to neighboring normal tissue and that mutation in the APC gene is directly linked to the expression of PGHS-2 in the tumors. Thus, prostaglandins play a major role in the development and progression of colon cancer but the mechanism is not clear. Some data suggest effects of prostaglandins are via modulation of apoptosis. We are examining arachidonic and linoleic acid metabolism,and the expression of PGHS-1 and -2, lipoxygenases, and cPLA2 in human cell lines. We observed, in SW-480 and other human colon cells that butyrate-induced differentiation results in an increased expression of PGHS-1 and a lipoxygenase. PGHS-2 expression is high in these cancer cells but expression is not altered by butyrate treatement. Butyrate also induces apoptosis but the addition of PGHS inhibitors did not alter the apoptosis in these cells. We are also using rat intestinal cell lines that highly express PGHS-2 and are used as a model of colon cancer. These studies will further define the potential use of NSAID as chemotherapeutic agents and hopefully better define the role of lipids in colon cancer.