| Background:Colorectal cancer is among the leading causes of cancer-related mortality, most patients were diagnosed in late stage, and the effects of operation on them were poor. Thus searching for effective drugs to the therapy, or those with potential to prevent colorectal cancer, is of great importance. Followed by the further understanding of relationship between chronic inflammation and tumor progression, nonsteroidal anti-inflammatory drugs (NSAIDs), as the main anti-inflammation drugs, draw more and more research attention for their functions of cancer therapy and chemoprevention. Ample data show that regular intake of NSAIDs is associated with decreased incidence of colorectal adenoma or colorectal cancer. NSAIDs have shown effects on tumor in many sites of the body through anti-proliferation and inducing apoptosis. Indomethacin has been frequently used to study the effect on colorectal cancer as well as cancers in other sites. Despite lots of researches related to NSAIDs including indomethacin's effect on CRC, concrete mechanism of its anti-tumor activity is not completely known. Because cyclooxygenase-2 (COX-2) is the main target through which NSAIDs exert their anti-inflammation effect, colorectal adenoma and adenocarcinoma have a high level expression of COX-2, and COX-2 specific inhibiting drugs such as celecoxib can impede cancer proliferation, so COX-2 has been thought to play a pivotal role in this process. However, COX-2 could not explain all the mechanism of NSAIDs' anti-cancer effects, other evidences exhibited that COX-independent cancer-chemotherapy mechanisms of NSAIDs still exist, since NSAIDs had antiproliferative effects on cell lines which do not expressed COX, anf derivations of NSAIDs which do not inhibit COX also have antitumor effects. Several studies have demonstrated that NSAIDs including indomethcin can play a chemopreventive and therapeutic activity through targets such as ribosomal S6 kinase 2 (RSK2), peroxisome proliferator-activated receptor...
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