Effects of a selective COX-2 inhibitor in patients with uterine endometrial cancers

Abstract

COX-2 is highly expressed in endometrial cancers, suggesting that a selective COX-2 inhibitor could be valuable for treating endometrial cancers that overexpress COX-2. In this study, we investigated the anti-tumor effects of the selective COX-2 inhibitor etodolac on endometrial cancer patients. Etodolac (400 mg, bid, for 2 weeks) was administered preoperatively to 21 endometrial cancer patients who had provided informed consent. Using pre-treatment biopsies and post-treatment surgical specimens, the expression levels of COX-2, Ki-67, p53, p21, p27, and cyclin D1 were evaluated by immunohistochemistry and the apoptotic index (AI) was determined by TUNEL staining. Preoperative biopsies and surgical specimens from 32 patients with endometrial cancer not treated with etodolac served as controls. Surgical specimens from COX-2 positive endometrial cancer patients treated with etodolac had significantly reduced expression levels of COX-2, Ki-67, p53, p21, p27, and cyclin D1 as determined by immunohistochemistry, while AI was not affected. These markers were unchanged for COX-2 negative endometrial cancer patients treated with etodolac and the control group. The selective COX-2 inhibitor etodolac showed anti-proliferative effects by suppressing COX-2 and cell-cycle regulator protein expression in patients with endometrial cancer positive for COX-2 expression. This study demonstrates that a selective COX-2 inhibitor is a potentially beneficial treatment for COX-2 positive endometrial cancers.