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

Med Oncol. 2010 Mar;27(1):98-104. doi: 10.1007/s12032-009-9179-y. Epub 2009 Feb 24.

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.

MeSH terms

  • Adenocarcinoma / blood supply
  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / 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
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Pyrazoles / administration & dosage*
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Cyclooxygenase Inhibitors
  • Pyrazoles
  • SC 560
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Dinoprostone
  • Cisplatin