| BackgroundCyclooxgenase (COX) enzymes catalyze the synthesis of prostaglandins (PGs) from arachidonic acid. The two isoforms of COX, COX1 and COX2, differ in many respects. COX1 is expressed constitutively in most tissues and appears to be responsible for the production of PGs that control normal physiological functions such as regulation of renal blood flow and maintenance of the gastric mucosa. By contrast, COX2 is not detected in most normal tissues. However, it is induced by mitogenic and inflammatory stimuli, which results in enhanced synthesis of PGs in neoplastic and inflamed tissues. In addition to the finding that COX2 is commonly overexpressed in premalignant and malignant tissues, there is considerable evidence that links COX2 to the development of cancer. The most specific data come from genetic studies. Transgenic mice that are engineered to overexpress COX2 increase the risk of tumor formation. Consistent with these studies, knocking out COX2 markedly reduces the development of tumors. These findings support a cause-and-effect connection between COX2 and tumorigenesis. The importance of arachidonic acid metabolism in tumorigenesis is underscored by the finding that knocking out COX1 also protects against the formation of tumors. In addition to genetic evidence, numerous pharmacological studies indicate that COX2 is a therapeutic target. Treatment with selective COX2 inhibitors reduces the formation of intestinal, esophageal, tongue, breast, skin, lung and bladder tumors in animals and also suppress the growth and metastasis of a variety of experimental established tumors. Epidemiological studies show that use of non-steroidal anti-inflammatorydrugs (NSAIDs), prototypic inhibitors of COX, is associated with a reduced risk of several malignancies, including colorectal cancer. Recently, overexpression of COX2 was found to increase the production and function of multidrug resistance (MDR1) in cells in culture. Coadministration of a selective COX2 inhibitor could overcome decrease in treatment efficacy by either chemotherapy or radiation. For the connection between COX and tumorigenesis, COX inhibitors, especially selective COX2 inhibitors, become the focus of the research. Numerous clinical trials are under way to assess the efficacy of the COX inhibitors in preventing tumors and the correlative Phase II studies are also ongoing. Recently, studies fasten on several typical drugs such as Celecoxib, so finding new material is a important problem. Matrine, Sodium Copper Chlorophyllin and Tamoxifen are the drugs which have been used in tumor therapy for a long time and have an acceptable risk-benefit profile. So in our study, we chose these materials as the targets of the primary selection for selective COX2 inhibitors. Matrine and Sodium Copper Chlorophyllin are the Chinese herbs which used in adjuvant tumor therapy. It has been proved that Matrine could induce proliferation and differentiation in K562 cell. Sodium Copper Chlorophyllin also has anti-mutation, anti-tumor effects. Tamoxifen is widely used in breast cancer therapy. Recently. Brodie investigated aromatase and COX2 were overexpression in tumors of the patients with estrogen-depend breast cancer. ProstaglandinE2 stimulated the synthesis of estrogen remarkably and using selective COX2 inhibitor could reduce the level of estrogen. As detailed above, Matrine, Sodium Copper Chlorophyllin and Tamoxifen all have anti-tumor effects. However, we yet have no idea about the relationship between the drugs' effects and COX. In this study, we investigate the effects of the drugs in low concentration on COX. The objective is to offer primary evidence for selective COX2 inhibitors selection and find new ways of these drugs clinical application. Method2 X 104 HT29 cells were inoculated in 96-well plate, set up 6 parallel team. Whenthe cells adhered completely, they were treated with the drugs except the blackcontrol group. After treatment for 12 hours, the cells' viabilities were determined by MTT assay.2 X 104 HT29 cells were inocul...
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