Cyclooxygenase-2 Silencing of MDA-MB-231 Breast Cancer Cells Reduces Invasion and Alters Metabolism

Tariq Shah¹, Ioannis Stasinopoulos¹, Flonne Wildes¹, Zaver M. Bhujwalla¹

To evaluate the role of cyclooxygenase-2 (COX-2) in human breast cancer cell proliferation and invasion we silenced COX-2 expression in the highly invasive MDA-MB-231 human breast cancer cells. Dynamic tracking of invasion and metabolism was performed with a magnetic resonance (MR) compatible cell perfusion assay under controlled pH, temperature, and oxygenation, over the course of 48 h. COX-2-silenced cells exhibited significantly reduced invasion relative to control cells expressing COX-2. COX-2 downregulation resulted in a significant reduction in choline kinase activity together with reduced total choline, phosphocholine and lactate levels consistent with the less malignant phenotype. Reduced expression of genes involved in invasion such as VEGF-A, MMP-2, and uPAR2 was observed in COX-2-silenced cells. Thus, silencing of COX-2 in MDA-MB-231 breast cancer cells resulted in reduced invasiveness as well as the acquisition of distinctive metabolism characteristics. These results suggest that COX-2 inhibition can effectively reduce tumor invasion and metastasis by poorly differentiated breast cancer cells.