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Effects of a cyclooxygenase-1-selective inhibitor in a mouse model of ovarian cancer, administered alone or in combination with ibuprofen, a nonselective cyclooxygenase inhibitor

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Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to be potent inhibitors of the cyclooxygenases. The present study was designed to investigate the effects of a cyclooxygenase (COX)-1 inhibitor, SC-560, administered alone or in combination with ibuprofen on the growth inhibition of s.c. human ovarian SKOV-3 carcinoma and on angiogenesis. The effects of SC-560 and ibuprofen on tumor growth inhibition have been examined in mouse ovarian cancer models. Angiogenesis of both COX inhibitors was measured by reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. Prostaglandin E2 (PGE2) levels in tumor tissues of mice were also determined by ELISA. The inhibitory rates in SC-560 group alone and in combination with ibuprofen group were 21.21% and 41.55%, respectively. In combination therapy with SC-560 and ibuprofen, tumor volumes were significantly reduced compared with that of control group (P < 0.05). In treatment groups, both COX inhibitors significantly reduced intratumor PGE2 levels (all P < 0.01). Microvessel density (MVD) in tumor tissues were significantly decreased from 80.90 ± 5.14 in vehicle-treated to 40.70 ± 10.45 and 38.90 ± 8.41 in SC-560 group alone and combination ibuprofen therapy (all P < 0.01). Ibuprofen was similar to the cyclooxygenase-1-selective inhibitor SC-560 in its ability to suppress the values of MVD of tumor tissues. SC-560 administered alone or in combination with ibuprofen inhibited the COX-associated up-regulation of VEGF. These studies demonstrate synergism between two COX inhibitors and that antiangiogenic therapy can be used to inhibit ovarian cancer growth.

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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Nanjing Medical University of Hangzhou Hospital, 310006, Hangzhou, China

    Wei Li & Zhen-yun Lin

  2. Department of Pathology, Nanjing Medical University of Hangzhou Hospital, 310006, Hangzhou, China

    Ru-jun Xu

  3. Department of Laboratory, Nanjing Medical University of Hangzhou Hospital, 310006, Hangzhou, China

    Guang-chao Zhuo & Hong-he Zhang

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Correspondence to Wei Li.

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Li, W., Xu, Rj., Lin, Zy. et al. Effects of a cyclooxygenase-1-selective inhibitor in a mouse model of ovarian cancer, administered alone or in combination with ibuprofen, a nonselective cyclooxygenase inhibitor. Med Oncol 26, 170–177 (2009). https://doi.org/10.1007/s12032-008-9104-9

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