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.
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.
Authors: C K Martin; W P Dirksen; M M Carlton; L G Lanigan; S P Pillai; J L Werbeck; J K Simmons; B E Hildreth; C A London; R E Toribio; T J Rosol Journal: Vet Comp Oncol Date: 2013-05-08 Impact factor: 2.613
Authors: A Heather Eliassen; Wendy Y Chen; Donna Spiegelman; Walter C Willett; David J Hunter; Susan E Hankinson Journal: Arch Intern Med Date: 2009-01-26
Authors: Julian A Abrams; Paul C Lee; Jeffrey L Port; Nasser K Altorki; Alfred I Neugut Journal: Cancer Epidemiol Biomarkers Prev Date: 2008-10 Impact factor: 4.254