COX-2 inhibitor celecoxib suppresses tumor growth and lung metastasis of a murine mammary cancer.
BACKGROUND: The antitumor growth and antimetastatic actions of celecoxib [a selective cyclooxygenase-2 ( COX-2) inhibitor] were investigated in a metastatic murine mammary cancer model. MATERIALS AND METHODS: Mice bearing mammary tumors, developed after inoculation of syngeneic BALBIc mice with a mammary carcinoma cell line carrying a p53 mutation, were treated with celecoxib at 0, 7.5 and 15 mg/kg five times a week for seven weeks. RESULTS: Tumor volumes were significantly reduced in association with an increase in apoptosis and a decrease in DNA synthesis in tumor tissues. In vitro studies demonstrated a significant increase in the number of cells undergoing apoptosis, with significantly elevated activities of caspase-3 and caspase-9, but not caspase-8, and a dose-dependent decrease in mitochondrial membrane potential, indicating the mitochondrial pathway of apoptosis. In addition, treatment with celecoxib showed cell cycle arrest in the G -phase and decreased cell population in the S- and G2/M-phases. Furthermore, tumor microvessel formation and mRNA levels for VEGF-A and COX-2 were markedly decreased. CONCLUSION: Celecoxib may be useful as an adjuvant therapy for breast cancer containing p53 mutations due to its ability to both induce p53-independent mitochondria-mediated apoptosis and exert anti-angiogenic potential.[1]References
- COX-2 inhibitor celecoxib suppresses tumor growth and lung metastasis of a murine mammary cancer. Yoshinaka, R., Shibata, M.A., Morimoto, J., Tanigawa, N., Otsuki, Y. Anticancer Res. (2006) [Pubmed]
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