Anticarcinogenic Activity Of NSAID Mediated By TGFB GENE

非类固醇抗炎药(NSAIDs)用于治疗炎症性疾病。近年来，非甾体类抗炎药被报道对人类结直肠癌的发生具有化学预防作用。非甾体抗炎药可抑制COX-1和/或COX-2活性，从而抑制前列腺素合成。然而，一些报道表明，对结肠癌的化学预防作用可能在一定程度上不依赖于前列腺素的抑制，可能依赖于基因表达。我们的目标是识别和表征受COX抑制剂调控的基因，包括选择性COX抑制剂。我们第一次尝试识别COX调控的基因，我们使用了一种基于PCR的方法。对人结肠癌细胞以及乳腺和肺癌细胞的治疗导致新基因(NAG-1，NSAIDs激活基因)的上调，我们已经鉴定了该基因是转化生长因子-β超家族基因的成员。本项目的主要目的有三：1)进一步研究非甾体抗炎药对NAG-1表达的影响，探讨促炎药物对NAG-1表达的影响；2)研究NAG-1基因启动子中的调控元件；3)通过细胞培养和动物模型研究NAG-1蛋白在细胞凋亡和炎症反应中的生物学功能(S)。我们还利用微阵列技术鉴定了选择性COX抑制剂诱导的基因，发现了一些受COX抑制剂诱导和抑制的基因。本研究可能为非类固醇抗炎药的抗结肠癌作用和抗炎作用提供新的见解和机制。

Non-steroidal anti-inflammatory drugs (NSAIDs) are used for the treatment of inflammatory diseases. Recently, NSAIDs have been reported to have a chemopreventive effect on the development of human colorectal cancer. NSAIDs can inhibit COX-1 and/or COX-2 activity and thus inhibit prostaglandin synthesis. However, some reports indicate that the chemopreventive effect on colon cancer may, in part, be independent of prostaglandin inhibition could dependent on gene expression. Our goal is to identify and characterize genes that are regulated by Cox inhibitors including selective Cox inhibitors. Our first attempt to identify Cox regulated genes we used a PCR base method. Treatment of human colon cancer cells as well as breast and lung cancer cells causes the up-regulation of novel gene (NAG-1, "NSAIDs activated gene") which we have characterized as member of the TGF-b superfamily gene. The project will be performed with three main aims; 1) to further characterize the expression of NAG-1 by NSAIDs and to explore the potential down regulation by pro-inflammatory agents, 2) to investigate the transacting elements in the NAG-1 gene promoter, 3) to identify of biological function(s) of NAG-1 protein in apoptosis and inflammation using cell culture and animal models. We have also use Micro-Array technology to identify gene induced by selective Cox inhibitors and have found a number of genes induced and suppressed by Cox inhibitor. The study may provide new insights and mechanisms for the attenuation of colon cancer and anti-inflammatory activity of NSAIDs.