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Effects Of Celecoxib On The Expression Of COX-2 And Survivin In Colon Cancer Xenograft Tumor In Nude Mice

Posted on:2009-05-18Degree:MasterType:Thesis
Country:ChinaCandidate:M Y XuFull Text:PDF
GTID:2144360245984884Subject:Surgery
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Objective: Cyclooxygenase-2 (COX-2), an induced en-zyme, participates the genesis and development of tumors by promoting proliferation, inhibiting of apoptosis, promoting an-giogenesis and inducing invasiveness. Survivin, a member of the inhibitor of apoptosis proteins (IAP) family, shows the strongest effect on inhibition of apoptosis. Survivin can be de-tected in almost all malignancies but rarely in normal differenti-ated adult tissues.Recent years, the incidence of colorectal cancer (CRC) is increasing, and CRC is one of threatens of the health and live of human in world, moreover COX-2 is overexpressed in at least 80 % of CRC. An animal experiment has indicated that non-steroidal anti-inflammatory drugs (NSAIDs) or selective COX-2 inhibitor could inhibit the development of inherited and azoxymethane-induced colon malignancy, thus it's significant to explore the mechanisms of selective cyclooxygenase-2 inhibitor in prevention and therapy of CRC.In present research, we generated HT-29 human colon cancer xenograft models by injecting HT-29 cells subcutane-ously into the back of nude mice, celecoxib, a specific COX-2 inhibitor, was administered, and the effects on COX-2, Survivin expression were evaluated.Method: Twelve 4~5 weeks old female BALB/c nude mice, whose weights were 20~24g respectively, were chosen and human colon cancer HT-29 cells (1×107/ml) were injected into the BALB/c nude mice subcutaneously (per mouse 0.2ml/). After injection, all nude mice were bred in SPF environment. the normal conditions of nude mice were observed every day and tumour volumes were measured every week. We also esti-mated the volumes of tumours with the formula—"V=ab2/2".After 16 days,mice were divided randomly into control group and celecoxib group. Celecoxib (40mg/kg) was intragas-tric administered in celecoxib group, and same volume distilled water was administrered in control group. Mice were sacrificed 30 days after the treatment. Xenograft cancer tissues were used to measure the expression level of COX-2 by immunohisto-chemistry, protein of Survivin by Western blot. COX-2 staining was mainly found in the cytoplasm which scattered as brown stain. After an overall review, we caught ten fields of vision randomly under a light microscope at 200-time magnification. Then we calculated the average optical density value. This ex-periment's measure data is expressed by mean±s, adopting SPSS 12.0 statistics software, chose two-group t-test, test levelα=0.05.Result: 1 The optical density of COX-2 in celecoxib group and control group was 15091.38±896.46 and 7862.12±847.72 respectively. COX-2 protein level in celecoxib group was sig-nificantly lower than that in control group (P < 0.001).2 Surivin protein level in celecoxib group was significantly lower than that in control group.Conclusions: 1 Celecoxib can suppress the expression of COX-2 and Survivin in colorectal carcinoma.2 It is possible that COX-2 was involved in the tumor for-mation and development of colorectal adenocarcinoma through promotion of Survivin.
Keywords/Search Tags:cycloxygenase-2, Survivin, xenograft tumor, celecoxib, colon adenocarcinoma
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