Impairment of breast cancer cell invasion by COX-2-specific inhibitor NS398: roles of CXCR4 and of uPA system Authors
First Online: 03 June 2011 Received: 05 May 2011 Accepted: 18 May 2011 DOI:
Cite this article as: Silva, H.C., Alves, V., Nogueira, L.A.M. et al. Med Oncol (2012) 29: 1468. doi:10.1007/s12032-011-9995-8
Inhibition of cyclooxygenase-2 (COX-2) is known to impair cancer cell metastatic behaviour, but the mechanisms involved largely remain elusive. We aimed to analyse whether the antimetastatic effect of COX-2 inhibition in breast cancer cells could be explained by variations in the expression levels of chemokine receptor CXCR4, vascular endothelium growth factor (VEGF) and UPA/UPAR components of the urokinase plasminogen activator system (uPAR). Breast cancer cell line MDA-MB-231 was exposed to COX-2-specific inhibitor NS398. Experimental data were assessed using Matrigel invasion tests, qRT-PCR, ELISA, flow cytometry and MTT test. Exposure to NS398 had no major effect on cell viability, apoptosis or VEGF production. Cell invasion was significantly decreased with reductions ranging from of 3.6% with 10 μM NS398 to 81.04% with 100 μM NS398. CXCR4 membrane expression was significantly reduced by 18% (
P < 0.05) when cells were treated with 100 μM of NS398 for 72 h. UPA mRNA levels were significantly reduced to 78 and 63% after treatment with 10 μM NS398 for 48 and 72 h, respectively ( P < 0.05). UPAR mRNA levels also decreased with mild NS398 concentrations, reaching the lowest level of 56% with 50 μM of NS398 for 48 h ( P < 0.05). With NS398 higher concentrations, UPAR and UPA expression levels increased. According to our results, impairment of expression of CXCR4, UPA and UPAR differentially contribute to the antimetastatic effect of COX-2 inhibitors depending on drug concentration.
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