Abstract
BackgroundBreast cancer is one of the most deadly diseases in women. Inhibiting the synthesis of estrogen is effective in treating patients with estrogen-responsive breast cancer. Previous studies have demonstrated that use of cyclooxygenase (COX) inhibitors is associated with reduced breast cancer risk.MethodsIn the present study, we employed an established mouse model for postmenopausal breast cancer to evaluate the potential mechanisms of the COX-2 inhibitor celecoxib. Aromatase-expressing MCF-7 cells were transplanted into ovariectomized athymic mice. The animals were given celecoxib at 1500 ppm or aspirin at 200 ppm by oral administration with androstenedione injection.ResultsOur results showed that both COX inhibitors could suppress the cancer xenograft growth without changing the plasma estrogen level. Protein expression of ERα, COX-2, Cyclin A, and Bcl-xL were reduced in celecoxib-treated tumor samples, whereas only Bcl-xL expression was suppressed in those treated with aspirin. Among the breast cancer-related miRNAs, miR-222 expression was elevated in samples treated with celecoxib. Further studies in culture cells verified that the increase in miR-222 expression might contribute to ERα downregulation but not the growth deterrence of cells.ConclusionOverall, this study suggested that both celecoxib and aspirin could prevent breast cancer growth by regulating proteins in the cell cycle and apoptosis without blocking estrogen synthesis. Besides, celecoxib might affect miR expression in an undesirable fashion.
Highlights
Breast cancer is one of the most deadly diseases in women
Effect of celecoxib and aspirin on xenograft growth Accelerated tumor growth was recorded in mice treated with androstenedione (AD) as compared with that of control mice (Control)
Expression of COX-2, cell cycle and apoptosis-related proteins in tumors Since both celecoxib and aspirin inhibited tumor growth in the animal model, we examined some proteins that are important in regulating cell growth
Summary
Breast cancer is one of the most deadly diseases in women. Inhibiting the synthesis of estrogen is effective in treating patients with estrogen-responsive breast cancer. Aspirin is a non-steroidal anti-inflammatory drug (NSAID) that inhibits both COX-1 and COX-2 It is capable of deterring the growth of breast cancer cells [11]. The COX-2 inhibitor reduces mammary tumor incidence induced by DMBA in rats [13] It is effective in blocking the growth of breast cancer xenografts in nude mice [14]. Celecoxib could evoke cell cycle arrest, anti-angiogenesis [15], and apoptotic cell death [16,17] in cancers. These NSAIDs appear to be chemopreventive, side effects like gastrointestinal tract bleeding [18] and cardiovascular toxicity [19] have been reported
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