| BackgroundOvarian carcinoma is a malignant tumor which is one of the most common malignant tumors in genital duct, and the onset of it is the most insidious. In the three female malignant tumors, the new patients of ovarian cancer are the second and the death ratio is the first one. Most patients have lost the chance of cure by operation when the disease is found, because they have already the symptom of intermediate stage and advanced stage, such as ascites, distant metastasis and so on. So the hard early diagnosis and the low five-year survival rate of ovarian cancer urge the medical worker to explore new diagnosis and treatment methods to prevent and to treat ovarian carcinoma.The study in colon carcinoma, breast carcinoma, and cholangiocarcinoma and so on found that the up-regulation of COX-2 and the inhibition of PPARγplay an important role in the development of carcinoma, and there were interaction between them. Furthermore, the immunohistochemistry result showed the existence of COX-2 over-expression and PPARγlow- expression in ovarian carcinoma. This implies that COX-2 and PPARγmay play an important role in the development of ovarian carcinoma. Celecoxib is a specific COX-2 inhibitor, which display its anti-inflammatory action through COX-2 pathway and antineoplastic action through COX-2 dependent and COX-2 independent pathway. Celecoxib may display its antineoplastic action through the activation of PPARγ. Celecoxib show off inhibit cell growth and proliferation, increase cell apoptosis, inhibit tumor invasion and metastasis, and cause G0/G1 cell cycle arrest.Pioglitazone is an artificial synthetically specific PPARγactivator. Pioglitazone may display its antineoplastic action through activate PPARγand transcript many kinds of cytokine and also though PPARγindependent pathway to anti-tumor. Pioglitazone inhibit tumorigenesis and tumor advancement through the inhibition of COX-2 partial activity. Pioglitazone cause the inhibition of tumor cell growth and proliferation, and increase cell apoptosis, and cause G1 cell cycle arrest, and inhibit tumor angiogenesis and invasion and metastasis.There are mutual effects between Celecoxib and Pioglitazone in the process of anti-tumor, so they may display anti-tumor actions together in cancer cells.This study observe the effects of different concentration of Celecoxib and Pioglitazone on the cell proliferation of the human ovarian carcinoma cell line SKOV3 and the expression of COX-2 mRNA in ovarian carcinoma cell, and explore the effects in the development of ovarian carcinoma, and provide theoretical evidence for its clinical therapy.ObjectiveTo explore the method which simultaneously target COX-2 and PPARγis whether more effective than use only one medicine, and provide theoretical evidence for its clinical therapy of ovarian carcinoma.Methods1. The effects in distinct time (24h, 48h, 72h) of different concentration (25μmol/l,50μmol/l,100μmol/l) of Celecoxib and Pioglitazone alone and combination on the cell proliferation of the human ovarian carcinoma cell line SKOV3 was measured by methabenzthiazuron (MTT) assay, and calculate the corresponding cell survival rate. 2. The effects of different concentration (25μmol/l,50μmol/l,100μmol/l) of Celecoxib and Pioglitazone alone and combinable on the expression of COX-2 mRNA in the human ovarian carcinoma cell line SKOV3 was detected by RT-PCR.Results1. After 24hr, 48hr and 72hr, Celecoxib (25μmol/l, 50μmol/l, 100μmol/l) or Pioglitazone (25μmol/l, 50μmol/l, 100μmol/l)dose dependently inhibited cell survival rate.2.Compared with single administration of Celecoxib or Pioglitazone, combination of them significantly decreased cell survival rate, P<0.05.3. After 72hr, Celecoxib (25μmol/l, 50μmol/l, 100μmol/l) or Pioglitazone (25μmol/l, 50μmol/l, 100μmol/l) dose dependently inhibited COX-2 mRNA expression level.4.Compared with single administration of Celecoxib or Pioglitazone , combination of them significantly decreased COX-2 mRNA expression level, P<0.05.Conclusion1. Combination of Celecoxib and Pioglitazone can inhibit cell proliferation more effective than single administration of Celecoxib or Pioglitazone.2. Combination of Celecoxib and Pioglitazone can inhibit COX-2 mRNA expression more effective than single administration of Celecoxib or Pioglitazone. |
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