Evaluation of anti-cancer activity of new COX-2 inhibitors in an invivo model of breast Cancer

Breast cancer is the second leading cause of death as a result of cancer among women, accounting for approximately 40,000 deaths each year. Current chemotherapy is unable to obtain clinical responses in patients with highly invasive metastatic disease. Therefore, there is an essentialneed for more effective approaches to prevention and treatment of breast cancer. An excellent currently available model of breast cancer is the BALB/c-derived 4T1 tumor. Cyclooxygenase-2 (COX-2) is a rate-limiting enzyme in the synthesis of prostaglandins. It is over-expressed in multiple cancers and has been associated with metastasis. In this study, the antitumor growth of celecoxib [a selective cyclooxygenase-2 (COX-2) inhibitor] as well as two new COX-2 inhibitor derivatives (A and B) were investigated in a murine mammary cancer model. Materials and Methods: Mice bearing mammary tumors, developed after inoculation of BALB/c mice with a mammary carcinoma cell line (4T1, 5 × 105), were treated with celecoxib and compounds A and B at 20 mg/kg (i.p) five times a week for four weeks. Results: Tumor volumes were significantly reduced in mice receiving 20 mg/ Kg of celecoxib and compounds A and B after 4 weeks. By the end of the experiment, the average tumor volume in control animals was 1002±49.27 mm3, while those for mice receiving celecoxib, compounds A and B were 183.5±49.50, 475.3±49.50 and 623.6±139.9 mm3, respectively.Conclusion: These studies suggest that celecoxib as well as compounds A and B can be good candidates for treating breast cancer. However compound A is more effective than compound B.

کلیدواژه ها:

Breast cancer ، Balb/c ، COX-2 ، 4T1 Cell