Role Of Lipids In Colon, Breast, And Other Cancers

花生四烯酸(AA)和亚油酸(LA)代谢的重要性得到了动物和人类流行病学研究的支持，这些研究表明，阿司匹林和其他抑制COX活性的非甾体抗炎药可以降低结肠癌的发病率和死亡率，并减少家族性息肉病患者的息肉。对啮齿动物的实验研究表明，非类固醇抗炎药可以减少致癌物诱导的结肠肿瘤的大小和数量。前列腺素和其他脂质在结肠癌和其他癌症的发生和发展中起着重要作用，但其机制尚不清楚。我们最近发现，在转基因小鼠胚胎发育过程中，COX-2的过度表达会导致许多生理缺陷，最终导致胎儿死亡。最显著的影响是通过诱导转基因胚胎的硬化体中的细胞凋亡而导致的骨骼发育。这是一种在其他组织中没有观察到的特异性反应。此外，在转基因胚胎中观察到P53蛋白的胞核积聚，提示COX-2可能通过上调P53的表达来诱导细胞凋亡。COX-2信号在胚胎发育过程中的异常是致畸的，提示COX-2可能与不明原因的胎儿畸形有关。

The importance of arachidonic acid (AA) and linoleic acid (LA) metabolism is supported by animal and human epidemiology studies that indicate that aspirin and other NSAIDs that inhibit COX activity, reduce the incidence and mortality of colon cancer and reduce 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. Prostaglandins and other lipids play a major role in the development and progression of colon and other cancers but the mechanism is not clear. We have recently discovered that the overexpression of COX-2 in a transgenic mouse model during embryonic development results in a number of physiological defects, ultimately resulting in the death of the fetus. The most dramatic effects were on skeletal development caused by the induction of apoptosis in the sclerotome of the transgenic embryos. This was a specific response not observed in other tissues. In addition, the sclerotomal accumulation of p53 protein is observed in transgenic embryos, suggesting that COX-2 may induce apoptosis via the up-regulation of p53. The aberrant COX-2 signaling during embryonic development is teratogenic and suggests a possible association of COX-2 with fetal malformations of unknown etiology.