نقش مهارکننده‌های انتخابی آنزیم Cox-2 بر ژن HIF-1 alpha در سرطان کولورکتال: یک مطالعه In vitro

Background: Colorectal cancer is a major cause of morbidity and mortality throughout the world, and its treatments include surgery, chemo-radiotherapy. Despite improvements in clinical outcomes of patients with this tumor over the past decades, prognosis remains poor with a 5-year survival rate of <10%. Angiogenesis inhibitor agents have been recently added to the treatment regimen of this disease. In the past two decades, it has been recognized that selective inhibitors of the cyclooxygenase -2 (Cox-2) enzyme result in the regression in the size of colorectal tumor, and one of its reasons is attributed to angiogenesis inhibition. The present study aimed at identifying the molecular pathways of angiogenesis inhibition by celecoxib. Methods: HCT-116, which is one of the cell lines of Colorectal cancer (separated from human colorectal adenocarcinoma) was provided by the National Cell bank of Iran (NCBI) affiliated to Pasteur Institute. It was then cultured in DMEM (high glucose) culture medium containing 10% FBS, and then treated in the active substance of celecoxib at pharmacological concentrations of 50 mM (C50) and 100 mM (C100). Afterwards, RNA was extracted and cDNA was prepared. The oligonucleotide of HIF-1 Alpha gene (angiogenesis initiator) was prepared and the level of HIF-1 alpha gene expression was assessed with a real-time PCR device in three control, C50 and C100 groups. Results: HIF-1 alpha gene expression significantly decreased in the celecoxib treatment group (compared with control group) with the concentration of C100 (P< 0.001), but no change was observed in the concentration of C50. Conclusion: Angiogenesis is a key factor in the carcinogenesis process and FDA today approved bevacizumab as a first-line treatment for patients with metastatic colorectal cancer. The results of this study showed one of the causes of angiogenesis reduction in celecoxib-treated colorectal cancer. According to clinical findings and basic studies, celecoxib will be hopefully used as a first-line therapy along with chemotherapy in the near future in colorectal cancer. The advantages of this treatment method include its low cost and low side effects.