期刊
TOXICOLOGY
卷 302, 期 2-3, 页码 190-196出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2012.07.015
关键词
Anorexia; Cyclooxygenase-2 (COX-2); Celecoxib; Chemotherapeutic agent; Interleukin-1 beta (IL-1 beta); Pro-opiomelanocortin (POMC)
资金
- Ministry of Education, Science, and Culture of Japan [23790598]
- Osaka Medical Research Foundation for Incurable Disease
- Osaka Cancer Society
- Grants-in-Aid for Scientific Research [23790598] Funding Source: KAKEN
Docetaxel, a taxane derivative, is frequently used for the treatment of advanced breast cancer, non-small cell lung cancer, and metastatic prostate cancer. Clinical reports demonstrated that docetaxel-based chemotherapy often induces anorexia, but the etiology is not completely understood. To elucidate possible mechanisms, we investigated the involvement of central interleukin (IL)-1 beta, cyclooxygenase (COX)-2, and pro-opiomelanocortin (POMC) in the development of docetaxel-induced anorexia in rats. Rats received docetaxel (10 mg/kg, i.p.) with or without pretreatment with selective COX-2 inhibitors, NS-398 (10 and 30 mg/kg, i.g.) or celecoxib (10 and 30 mg/kg, i.g.), and a non-selective COX inhibitor, indomethacin (10 mg/kg, i.g.), then food intake was monitored for 24h after administration. We also examined expression of IL-1 beta, COX-2, and POMC mRNA in hypothalamus of docetaxel-treated rats and the effect of a COX-2 inhibitor on docetaxel-induced POMC mRNA expression. Food consumption in rats was significantly decreased 24h after administration of docetaxel and anorexia was partially reversed by all COX inhibitors. Administration of docetaxel increased IL-1 beta, COX-2, and POMC mRNA expression in the hypothalamus of rats. The time required to increase these gene expressions was comparable to the latency period of docetaxel-induced anorexia in rats. In addition, pretreatment with COX-2 inhibitors suppressed docetaxel-induced expression of POMC mRNA. These results suggest that IL-1 beta and COX-2 mRNA expression and subsequent activation of POMC in the hypothalamus may contribute to the development of docetaxel-induced anorexia in rats. (C) 2012 Published by Elsevier Ireland Ltd.
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