Effects of a selective cyclooxygenase-1 inhibitor in SKOV-3 ovarian carcinoma xenograft-bearing mice.
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.
Li
Wei
W
Department of Gynecology and Obstetrics, Nanjing Medical University of Hangzhou Hospital, Hangzhou, China. wei5901482@tom.com
Ji
Zhong-lei
ZL
Zhuo
Guang-chao
GC
Xu
Ru-jun
RJ
Wang
Jie
J
Jiang
Hong-ru
HR
D000230:Adenocarcinoma / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage; D051545:Cyclooxygenase 1 / Q000096:biosynthesis; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011720:Pyrazoles / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; C115461:SC 560; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D002945:Cisplatin