Anti-carcinogenic Activity Of Cox inhibitors and NAG-1

非甾体抗炎药（NSAID）用于治疗炎症性疾病。最近，NSAIDs已被报道对人类结直肠癌的发展具有化学预防作用。NSAID可抑制考克斯-1和/或考克斯-2活性，从而抑制前列腺素合成。然而，一些报告表明，对结肠癌的化学预防作用可能部分不依赖于前列腺素抑制，可能依赖于基因表达。我们的目标是鉴定和表征受包括选择性考克斯抑制剂在内的考克斯抑制剂调控的基因。用NSAID治疗人类癌细胞引起新基因NAG-1或NSAID激活基因的上调，该基因是TGF-β超家族基因的成员。该项目有三个目标：1）进一步表征NSAID和其他药物对NAG-1的表达，2）研究NAG-1基因启动子中负责调控的反式作用元件，3）鉴定NAG-1与癌症和炎症相关的生物学功能。

Non-steroidal anti-inflammatory drugs (NSAIDs) are used for the treatment of inflammatory diseases. Recently, NSAIDs have been reported to have chemopreventive effects 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. Treatment of human cancer cells with NSAIDs caused the up-regulation of novel gene NAG-1, or NSAIDs activated gene that is member of the TGF-b superfamily gene. The project has with three aims; 1) to further characterize the expression of NAG-1 by NSAIDs and other drugs,2) to investigate the transacting elements in the NAG-1 gene promoter responsible for the regulation, and 3) to identify of biological function(s) of NAG-1 as related to cancer and inflammation.