Study On The Correlation Between Cyclooxygenase-2 Protein And Multidrug Resistance In Gastric Carcinoma

Background:The incidence of gastric cancer has increased rapidly. Prognosis of gastric cancer is depressing with 5-yr survival of less than 15-20%. Multi-drug resistance(MDR) is the biological basis of refractory gastric cancer. Searching for an efficient reversing agent of MDR is always important in the clinical cancer research. In recently ten years, some epidemiological studies have indicated that nonsteroidal anti-inflammatory drugs(NASAIDs) could reduce the risk of cancer, especially in gastrointestinal carcinogenesis, one possibility is that NSAIDs inhibit expression of Cyclooxygenase-2 (COX-2). Cyclooxygenase (COX) is the rate-limiting enzyme for the high output production of Prostaglandins from arachidonic acid. Many findings show that the isoformate COX-2 is involved in progression of gastrointestinal carcinogenesis through many ways. Recently research indicated that COX-2 may relate to MDR, it will not only enrich the evidence that COX-2 is associate with cancer, but also be a new target for cancer prevention and treatment. Objcctive:To investigate the cyclooxygenase-2(COX-2) expressions in gastric carcinoma and investigate the effects of COX-2 expression on P-glycoprotein, we took gastric carcinoma cells as targets to study the activity of COX-2 inhibitor partial reversing effect upon MDR of cancer and its effect on the expression of P-glycoprotein . To indicate the role of COX-2 in gastric carcinoma and COX-2 take part in mediation of multidrug-resistant (MDR) in gastric carcinoma. Method:1. Using immunohistochemistry to investigated expressions of COX-2 and P-gp in specimen of gastric cancer and control in endoscopic biopsies.2. Takeing human gastric cancer cell line resistant to vincristine (SGC7901/VCR) as targets to investigate COX-2 inhibitor Partial reverseing effect on multidrug resistance of SGC7901/VCR andmechanism was measured by flow cytometry> MTT and immunohistochemistry . Result1. The positive expression rate of COX-2 was 60.4% higher in gastric carcinoma, we find that P-glycoprotein expression rate in COX-2 positive expression group was 82.8%, and 63.2% of P-glycoprotein was not express in COX-2 negative expression group. The over-expressions of COX-2 was significantly correlation with P-glycoprotein . The correlation coefficient was r=0.470 (PO.01).2. MTT analyzed that celecoxib was able to inhibit the growth of SGC7901, SGC7901 /VCR cells in a dose-and time-dependent manner in vitro; After exposure of SGC7901/VCR cells with non-cytotoxic dose of celecoxib (2.5umol/l), the sensitivity of target cells to chemotherapeutical agents was remarkably increased, indicating that the MDR of SGC7901/VCR cells was partly reversed. The reversal times varied from 1.09 to 6.28; With the help of flowcytometry. We found increase of illtracellular concentration of adriamycin in SGC7901/VCR cells during celecoxib mediated reverse of MDR. Immunocytohistochemistry showed over-expression of P-glycoprotein in SGC7901/VCR cells was decreased after exposure to the celecoxib.Conclusion1. The expression of COX-2 is involved in progression of gastrointestinal carcinogenesis and might take part in mediation of MDR in gastric carcinoma.2. Celecoxib was able to significantly inhibit the growth of tumor cells, and it can partly reverse MDR of SGC7901/VCR cells through interfering the PI70 expressions.