Inhibitory Effects Of COX-2 Selective Inhibitor Combined With 5-Fu On Growth Of Gastric Cancer

IntroductionGastric cancer is a most common malignant tumor, and its survival rate of 5 year is only 20% . 5 - Fu is the basical drug for the chemotherapy of gastric cancer, which response rate is 21 % , but it induces resistance readily, and reduces efficacy, it is necessary to find a new assistant drug to increase its effect. Recently a lot of reports show that COX - 2 may relate to the occurance, and development of cancer. It is identified that COX - 2 is up - regulated in many cancers, such as colon cancer, gastric cancer, Barretts esophagus, esophageal, and the cancer of head and neck. But Cox - 1 has no significant change. COX - 2 expresses highly in many kinds of cancer tissues, but has poor expression or no expression in nomal tissue. Epidemiological studies show that administration of NSAIDs can reduce the incidence of colon cancer, gastric cancer, and esophageal cancer. NSAIDs exert the effect of febrifuge and ease pain through inhibiting COX -1 and COX -2. The selective inhibitor of COX -2 is a new NSAIDs , which reduce synthesis of PGE through inhibiting COX - 2 selectively and escape the complications of degistive tract. Now study shows that NSAIDs have an-ticancer effect and can inhibit the proliferation of tumor cell, and induce apopto-sis, but its mechanism is not clear. Now the debation focus on COX - 2 dependent and COX - 2 non - dependent pathway. The present study is to research the effect of inhibitor of COX - 2 on 5 - Fu chemotherapy through combination of NS398 and 5 - Fu, and explore its mechanism.Materials and Methods1. Cell cutureThe gastric cancer cell line MGC -803 was cutured in RPMI - 1640 sup -plemented with 10% (v/v) heated - inactived fetal bovine serum contai ning 12u/ml gentamycin and incubated at 37℃ in 5% CO₂ atmosphe re. In all experiments, cells were used in logarithmic growth phase.2. Assays for proliferation of MGC - 803 cell. Cell proliferation was determined by MTT.3. Assays for cell cycle arrest and apoptosisThe morphological change was observed by microscope and dyed in Wrighe Giemsa,and determined by flow cytometric analysis.4. ImmunocytochemistryThe expression of COX - 2 protein was determined by immunocytochem -istry.5. Statistical analysisAll of the data were analyzed by spssll. 5Results1.4uM NS398 has low cytotoxity and the inhibitory rate of 24h, 48h was 17.03% ,20.20% repectively.2. The IC50 of 24h, 48h are 6.3ug/ml, 2.5ug/ml respectively, when 5 -Fu is administrated alone. The IC50 of 24h, 48h are 0.74ug/ml,0.29ug/ml re-sp - ectively, when 5 — Fu is administrated with NS398.3. The apoptosis rate of MGC -803 is 3.65% when it is untreated. The apoptosis rate of MGC - 803 is 18. 88% , when it is treated by 5 - Fu alone. The apoptosis rate of MGC - 803 is 18. 71% , when it is treated by 5 - Fu with NS398.4. The expression rate of COX -2 is 68. 5% in MGC -803 cell. It is 26. 5% when NS398 was administrated alone. 5 - Fu can down - regulate COX -2...