Celebrex
Shows Promise for Reducing Tumor Mass in Breast Cancers
Behind the Cancer Headlines®
The anti-inflammatory drug Celebrex, or celecoxib, reduces tumor mass by encouraging cell death and discouraging both cell proliferation and the sprouting of new blood vessels that feed growing tumors, according to a study reported in the journal Molecular Cancer Research.
The study, conducted by researchers at the Mayo Clinic College
of Medicine in
"This COX-2 inhibitor represents a strong option for treatment of breast cancers, and a preventative agent for treatment of individuals with high risk of developing breast cancer or disease relapse," said Pinku Mukherjee, Ph.D., the senior author of the report.
The Mayo study showed that celecoxib caused reduction in mammary gland tumor mass that was associated with increased programmed cell death, or apoptosis, in the breast tissue of the mice. Celecoxib-induced cell death was associated with two molecular events involving pathways that lead to apoptosis. The COX-2 inhibitor increased expression of the Bax protein, which is known to function within the pro-apoptotic cell mechanism. Further, the introduction of celecoxib resulted in reduced activity of an anti-apoptotic protein, Akt, known to promote cell survival.
Generally, COX-2 works by regulating the production of prostaglandins in cells. In the Mayo study, celecoxib reduced levels of COX-2 protein in mammary tumor cells; the therapy was even more effective in minimizing the amounts of COX-2 dependent prostaglandin E metabolites in mammary tumor cells.
"Celecoxib treatment appears to exert its antiproliferative, antiangiogenic, and pro-apoptotic effects by regulating the prostaglandin pathways," Mukherjee said. "This leads to the reduction in primary breast tumor mass."
She noted that in an experiment with a limited number of mice, celecoxib appeared to completely inhibit metastasis of the breast tumor.
The study employed a mouse model system that closely resembles spontaneous breast cancer progression and metastasis in humans.
"The
MTag
mouse model for human
metastatic
breast cancer is a helpful and important model in which to evaluate therapeutic
strategies and to understand the mechanisms associated with therapy-induced
growth inhibition," said
Mukherjee. "This model allows us to proceed with
preclinical studies that must precede clinical trials in order to enable us to
develop efficient therapeutic strategies with targeted molecular therapies."
SOURCES:
Molecular Cancer Research, November 2004
American Association for Cancer Research (http://www.aacr.org)