Celecoxib in breast cancer prevention and therapy

Abstract

Breast cancer has a high incidence worldwide. The results of substantial studis reveal that inflammation plays an important role in the initiation, development, and aggressiveness of many malignancies. The use of celecoxib, a novel NSAID, is repetitively associated with the reduced risk of the occurrence and progression of a number of types of cancer, particularly breast cancer. This observation is also substantiated by various meta-analyses. Clinical trials have been implemented on integration treatment of celecoxib and shown encouraging results. Celecoxib could be treated as a potential candidate for antitumor agent. There are, nonetheless, some unaddressed questions concerning the precise mechanism underlying the anticancer effect of celecoxib as well as its activity against different types of cancer. In this review, we discuss different mechanisms of anticancer effect of celecoxib as well as preclinical/clinical results signifying this beneficial effect.

MAGI1, a New Potential Tumor Suppressor Gene in Estrogen Receptor Positive Breast Cancer

“…We have previously reported similar observations in colorectal cancer cells [4]. Considering that chronic inflammation is associated with an increased risk of cancer incidence and progression [65], this is a highly clinically relevant observation. COX-2, the rate-limiting enzyme in PGE 2 synthesis, is overexpressed in several cancers including BC [53,57].…”

“…PGE2 stimulates tumor cell proliferation, invasion, and angiogenesis, inhibits tumor cell apoptosis, and promotes immunosuppression [54,66,67]. Preclinical and clinical studies showed that nonsteroidal anti-inflammatory drugs (NSAIDs) have chemopreventive effects on several cancers including BC [68][69][70], and exert anti-tumor activities, and in particular ketorolac when administrated in the peri-operative setting [65,71]. However, their routine use as adjuvant treatment in BC is still inconsistent and not yet recommended [72][73][74][75][76][77][78][79].…”

Celecoxib, a selective COX‑2 inhibitor, markedly reduced the severity of tamoxifen‑induced adenomyosis in a murine model

“…The interpretation of this finding with regard to the antiangiogenic effects of celecoxib in this model is limited. In view of the angiogenesis effect of the increased expression or activity of Cox-2, recently the inhibition of Cox-2 by celecoxib has been explored to be used in the treatment of diverse cancers such as breast cancer and hepatocellular carcinoma (18,53,54). So further should be performed in larger sample populations or in vitro to reveal the association between the inhibition of Cox-2 by celecoxib and angiogenesis, which may provide a more solid theoretical basis for the application of celecoxib for the treatment of adenomyosis.…”

“…Findings from recent studies have suggested that NSAIDs are also capable of inhibiting angiogenesis, proliferation, the expression of aromatase P450 and epithelial-mesenchymal transition (EMT) in numerous cancer models, such as colorectal cancer, prostate cancer and human glioblastoma endothelial cells, highlighting their potentially novel properties (12)(13)(14). Additionally, the long-term use of NSAIDs has been proposed as a therapeutic Celecoxib, a selective COX-2 inhibitor, markedly reduced the severity of tamoxifen-induced adenomyosis in a murine model strategy for a number of malignancies, including prostate, colon and breast cancer (15)(16)(17)(18).…”

NF-κB and Its Role in Checkpoint Control

“…COX-2 suppression by Andro resulted in the inhibition of tumor growth and tumor angiogenesis in a murine breast cancer model ( Figure 2) [140]. Celecoxib is another well described specific inhibitor of COX-2, which has also been shown to inhibit IKK activity and to have anti-tumor effects in various human cancers [123,141]. Zuo and colleagues showed that celecoxib inhibits expression of NF-κB in a concentration dependent manner in pancreatic cancer cells.…”