Targeting of COX-2 Expression by Recombinant Adenovirus shRNA Attenuates the Malignant Biological Behavior of Breast Cancer Cells

Background: Cyclooxygenase-2 (COX-2), considered to have tumor-promoting potential, is highly expressedin a variety of tumors, including breast cancer. Since the functions and action mechanisms of COX-2 in breastcancer have not been fully elucidated, in the present study, the effects of target inhibiting COX-2 with recombinantadenovirus Ad-COX-2-shRNA on malignant biological behavior were investigated in representative cell lines.Materials and
Methods: Breast cancer MDA-MB-231 and MCF-7 cells were transfected with Ad-COX-2-shRNAand COX-2 expression was tested by RT-PCR and Western blotting. Changes in proliferation, apoptosis andinvasion of breast cancer cells were detected with various assays including MTT, colony forming, flowcytometryand Transwell invasion tests. The expression of related proteins involved in the cell cycle, apoptosis, invasionand signaling pathways was assessed by Western blotting.
Results: COX-2 expression was significantly reducedin both breast cancer cell lines infected with Ad-COX-2-shRNA, with obvious inhibition of proliferation,colony forming rate, G2/M phase passage and invasion, as well as induction of apoptosis, in MDA-MB-231 andMCF-7 cells, respectively. At the same time, proteins related to the cell cycle, anti-apoptosis and invasion weresignificantly downregulated. In addition, c-myc expression and phosphorylation activation of Wnt/β-cateninand p38MAPK pathways were reduced by the Ad-COX-2-shRNA.
Conclusions: COX-2 expression is associatedwith proliferation, apoptosis and invasion of breast cancer cells, and its mechanisms of action involve regulatingexpression of c-myc through the p38MAPK and Wnt/β-catenin pathways.