The effectiveness of cyclooxygenase-2 inhibitors and evaluation of angiogenesis in the model of experimental colorectal cancer

ABSTRACT THE EFFECTIVENESS OF CYCLOOXYGENASE-2 INHIBITORS AND EVALUATION OF ANGIOGENESIS IN THE MODEL OF EXPERIMENTAL COLORECTAL CANCER Colorectal cancer (CRC) is an important cause of cancer-related deaths worldwide. Early diagnosis and treatment of CRCs are of importance for improving survival. In the present study, it was aimed to investigate effects of COX-2 inhibitors on tumor development incidence and angiogenesis in Sprague Dawley rats in which an experimental model of CRC was created. Rats were divided into 4 groups. Control group received 1 mM EDTA saline (SC, weekly) for 12 weeks and DMSO (PO, daily) throughout experiment (25 weeks). DMH group received 25 mg/kg DMH in 1 mM EDTA-saline (SC, weekly) for 12 weeks and DMSO (PO, daily) for 25 weeks. The groups received 8 mg/kg diclofenac and 6 mg/kg celecoxib in DMSO (PO, daily) simultaneously with DMH throughout experiment were identified as treatment groups. The rats were sacrificed by decapitation at the end of experiment. Histopathological and immuno histochemical evaluations were performed in colorectal tissue samples, whereas angiogenesis parameters were studied in blood samples. In histopathological evaluations, no pathological change was observed in control rats, while adenocarcinoma (62,5%), dysplasia (31,25%) and inflammation (6,25%) were detected in DMH group. In treatment groups, a marked decrease was observed in adenocarcinoma rate. When compared to controls, a significant increase was detected in VEGF, ICAM-1, MMP-2, and MMP-9 levels and MMP-2/TIMP-2 ratio in DMH group. When compared to DMH group, a significant decrease was detected in MCP-1 level and in all above-mentioned parameters, while a significant increase in TIMP-2 levels in celecoxib group. In immunohistochemical studies, there was an increase in intensity and extent of staining of MMP-2, MMP-9 and NFκ-B in DMH group when compared to controls, while a decrease in treatment groups when compared to DMH group. The decrease in celecoxib group was more prominent. In conclusion, it was comfirmed by immunohistochemical, histopathological and biochemical evaluation results that NSAI drugs, particularly COX-2 inhibitors, decrease rate of disease and slow down progression of existing disease in CRCs. Keywords: Colorectal cancer, angiogenesis, COX-2 inhibitors, NSAI drugs