| Epidemiological studies have shown a reduced rate of genesis and mortality from colorectal cancer in the population of patients who take nonsteroidal anti-inflammatory drugs(NSAIDs) on a regular basis compared with the population not taking NSAIDs, and It had a strong relationship with NSAJDs dose. NSAIDs have also shown chemopreventive effects as judged by reduction in the size and the number of tumor in rodent model of chemically induced colon cancer. It's not entirely clear how this protective effect of NSAIDs is exerted but a number of studies have strongly implicated that NSATDs play a role for inhibition of COX-2 in tumor prevention. It's well known that cyclooxygenase is expressed in mammalian cells in two distinct isoforms : COX-1 and COX-2. Cox-1 gene is a constitutively expressded one that related to housekeeping function in most tissue and it mediates the synthesis of PGs required for normal physiological function ,such as gastric secretion.gastric mucosa protection,regulation of renal function,platelet agglutination,and blood vessel tension. Cyclooxygenase-2 gene is regarded as a rapidly response gene and its expression can be elevated induced by inflammation,ulcer ,various tumor and many regulatory factors such as cytokines,tumor necrosis factor- a (TNF- a), interleukin-6 (EL-6),bacterial endiotoxin,growth factors,platelet derived growth factor(PDGF) and etc. It also plays a role in some pathological process such as inflammation,carcinogenesis and etc. Recently there is increasing attention to relationship between COX-2 and tumorgenesis. Immunohischemistry and RT-PCR results showed that COX-2 mRNA and protein but not COX-1 wereelevated compared with normal tissue in colorectal adenomas,colorectal adenocarcinoma,gastric cancer and pancreatic cancer ,lung cancer ,prostatic cancer and osteogenic sarcoma .COX-2 is a new therapeutic target of inhibiting cancer.NSAIDs produce their therapeutic benefits by inhibiting COX-2 at the site of inflammatory ,while resulting in a series serious adverse effects such as PUBs(perforate, ulcer, bleeding), disorder of liver function and renal function COX-1 in the gastric mucosa and other tissues and organs as a result of COX -1 inhibition. Because of their side effects, NSAIDs is limited in treatment.lt was found that amino acid sequences in active site of COX-2 is different from those of COX-1. The two isoforms can be founded in different tissues .Thus it is possible to find some subjects which inhibit COX-2 selectively.These subjects are named as selective COX-2 inhibitor including nimesulide ,rofecoxib,celecoxib , meloxicam, NS-398 and so on. Recently selective COX-2 inhibitor have been developed and introduced to man for the treatment of osteoarthritis and rheumatic arthritis . It is reported that these selective COX-2 inhibitors have similar therapeutic benefits and adverse effects compared with traditional NSAIDs and placebo respectively. Moreover recently increasing evidence suggests that COX-2 inhibitors may have important therapeutic relevance in the prevention of some cancer, colorectal cancer as a example.In present studies, we investigated the expression of COX-2 in SGC7901, 7901-P,7901-AS and the relationship between COX-2 and cell proliferation,cell cycle, apoptosis, and rumorgenesis. We also investigated the effects of NSAIDs on gastric cancer cell. PUBs were detected in nude mice administered NSAIDs. The segment of liver,kidney,stomach,duodenum were investigated by HE staining. We aimed to judge the therapeutic benefits and adverse effects and single out some NSAIDs that have maximum benefits but minimum side effects for prevention and treatment of gastric cancer. The results are summarized asfollows.1. Immunohistochemistry showed positive staining of COX-2 protein in human gastric cancer cell line SGC790K 7901-P while the COX-2 staining was weak in 7901-AS.2. Some of NSAIDs in the studies,celecoxib as a highly selective COX-2 inhibitor especially, had revealed a role of inhibiting cell proliferation and activity of...
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