Abstract
BackgroundDuring the last few years it has been shown in several laboratories that Celecoxib (Cx), a non-steroidal anti-inflammatory agent (NSAID) normally used for pain and arthritis, mediates antitumor and antiangiogenic effects. However, the effects of this drug on a tumor cell line resistant to chemotherapeutical drugs used in cancer have not been described.Herein we evaluate the angiogenic and antitumor effects of Cx in the development of a drug-resistant mammary adenocarcinoma tumor (TA3-MTXR).ResultsCx reduces angiogenesis in the chick embryonic chorioallantoic membrane assay (CAM), inhibits the growth and microvascular density of the murine TA3-MTXR tumor, reduces microvascular density of tumor metastases, promotes apoptosis and reduces vascular endothelial growth factor (VEGF) production and cell proliferation in the tumor.ConclusionThe antiangiogenic and antitumor Cx effects correlate with its activity on other tumor cell lines, suggesting that Prostaglandins (PGs) and VEGF production are involved. These results open the possibility of using Celecoxib combined with other experimental therapies, ideally aiming to get synergic effects.
Highlights
During the last few years it has been shown in several laboratories that Celecoxib (Cx), a non-steroidal anti-inflammatory agent (NSAID) normally used for pain and arthritis, mediates antitumor and antiangiogenic effects
Celecoxib (Cx) is a selective COX-2 inhibitor approved by the Food and Drug Administration (FDA) for rheumatoid arthritis, osteoarthritis and acute pain, but in the last years it has been proposed as an agent that can intervene signal transduction pathways associated with COX-2 expression and increase the levels of endogenous inhibitors of angiogenesis, called endostatins [6,7]
Cx inhibits the growth of a meningioma in vivo, decreases COX-2 activity and lowers PG concentrations and angiogenesis, promoting higher rates of apoptosis [4]
Summary
During the last few years it has been shown in several laboratories that Celecoxib (Cx), a non-steroidal anti-inflammatory agent (NSAID) normally used for pain and arthritis, mediates antitumor and antiangiogenic effects. Celecoxib (Cx) is a selective COX-2 inhibitor approved by the Food and Drug Administration (FDA) for rheumatoid arthritis, osteoarthritis and acute pain, but in the last years it has been proposed as an agent that can intervene signal transduction pathways associated with COX-2 expression and increase the levels of endogenous inhibitors of angiogenesis, called endostatins [6,7]. NSAIDs decrease tumor progression for some malignancies such as colon cancer [8,9,10] For this reason, Cx has been proposed for the treatment of colon, pancreatic, and breast cancer, suppressing angiogenesis and promoting apoptosis [5,10,11]. Cx inhibits the growth of a meningioma in vivo, decreases COX-2 activity and lowers PG concentrations and angiogenesis, promoting higher rates of apoptosis [4]
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