Effects of a selective cyclooxygenase-1 inhibitor in SKOV-3 ovarian carcinoma xenograft-bearing mice

• DOI: 10.1007/s12032-009-9179-y
• Publication Date: 2009-02-23T11:53:58Z
• Authors: Wei Li; Zhong-lei Ji; Guang-chao Zhuo; Ru-jun Xu; Jie Wang; Hong-ru Jiang
• Keywords: Ovarian Neoplasms; Neovascularization, Pathologic; Antineoplastic Agents; Adenocarcinoma; Immunohistochemistry; Xenograft Model Antitumor Assays; Dinoprostone; 3. Good health; Mice; 03 medical and health sciences; 0302 clinical medicine; Cyclooxygenase 2; Cell Line, Tumor; Cyclooxygenase 1; Animals; Humans; Pyrazoles; Cyclooxygenase Inhibitors; Female; Cisplatin

To evaluate the effect of a cyclooxygenase-1 (COX-1) inhibitor, SC-560, on the growth inhibition of s.c. human ovarian SKOV-3 carcinoma and on angiogenesis. Human ovarian SKOV-3 carcinoma cells xenograft-bearing mice were treated with SC-560, a COX-1-selective inhibitor, 6 mg/kg alone i.g. daily, and i.p. injections of cisplatin 3 mg/kg every other day for 21 days. Prostaglandin E(2) (PGE(2)) levels were determined by ELISA. Microvessel density (MVD) of ovarian carcinoma was determined with anti-CD(34) as the label by immunohistochemistry. In addition, the expression of COX-1 at protein levels in the control group was detected by immunohistochemistry. SC-560 reduced the growth of tumors when SKOV-3 cells were xenografted in nude female mice. The inhibitory rates in SC-560 group and cisplatin group were 47.1% and 51.7%, respectively, which is significant statistically compared to that of control group (all, P < 0.05). In treatment groups, SC-560 significantly reduced intratumor PGE(2) levels (P < 0.01). MVDs in SC-560 group were 35.73 +/- 9.87, which are significant statistically compared to that of control group (74.33 +/- 9.50) (P < 0.01). COX-1, not COX-2, protein levels are elevated in tumor tissues. These findings may implicate COX-1 as a suitable target for the treatment of ovarian cancer and that antiangiogenic therapy can be used to inhibit ovarian cancer growth.