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

Abstract
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.
AuthorsWei Li, Zhong-lei Ji, Guang-chao Zhuo, Ru-jun Xu, Jie Wang, Hong-ru Jiang
JournalMedical oncology (Northwood, London, England) (Med Oncol) Vol. 27 Issue 1 Pg. 98-104 (Mar 2010) ISSN: 1559-131X [Electronic] United States
PMID19235530 (Publication Type: Journal Article)
Chemical References
  • Antineoplastic Agents
  • Cyclooxygenase Inhibitors
  • Pyrazoles
  • SC 560
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Dinoprostone
  • Cisplatin
Topics
  • Adenocarcinoma (blood supply, drug therapy, metabolism, pathology)
  • Animals
  • Antineoplastic Agents (administration & dosage)
  • Cell Line, Tumor
  • Cisplatin (administration & dosage)
  • Cyclooxygenase 1 (biosynthesis)
  • Cyclooxygenase 2 (biosynthesis)
  • Cyclooxygenase Inhibitors (administration & dosage)
  • Dinoprostone (biosynthesis)
  • Female
  • Humans
  • Immunohistochemistry
  • Mice
  • Neovascularization, Pathologic (drug therapy)
  • Ovarian Neoplasms (blood supply, drug therapy, metabolism, pathology)
  • Pyrazoles (administration & dosage)
  • Xenograft Model Antitumor Assays

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