Novel COX-2 Inhibitor for Breast Cancer Therapy

摘要

Recent studies have shown that NSAIDS reduce the incidence of human cancers by inhibiting COX enzymes. Of these, the COX-2 isoform has been shown to be constitutively overexpressed in many tumor types, including those of the breast. The purpose of this study was to develop novel COX-2 inhibitors that can be used in breast cancer therapy. We have developed several classes of novel COX-2 inhibitors that inhibit the growth of both COX-2 positive and negative tumor cell lines, suggesting that they may target other protein(s) that play an important role in tumor cell proliferation. We have also determined that our most potent COX-2 inhibitor, which is nearly 6-fold more active than celecoxib, induced irreversible G1 arrest of tumor cells and ultimately led to tumor cell apoptosis. We have also determined the mechanism of action of these COX-2 inhibitors, which suggest an important role for these compounds as anti-cancer agents.