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- Title
Oxaliplatin induces prostaglandin E2 release in vascular endothelial cells.
- Authors
Matsunuma, Satoru; Handa, Satoko; Kamei, Daisuke; Yamamoto, Hitomi; Okuyama, Kiyoshi; Kato, Yasuhisa
- Abstract
<bold>Purpose: </bold>Oxaliplatin (L-OHP) is known to induce adverse reactions at the injection site, including vascular pain, but the underlying mechanisms have not been clarified. Vascular pain during intravenous L-OHP administration can be inhibited by taking non-steroidal anti-inflammatory drugs (NSAIDs). In this study, we investigated the involvement of the arachidonic acid cascade and prostaglandin (PG) E2 and 15d-PGJ2 in vascular pain sensation during intravenous delivery of L-OHP.<bold>Methods: </bold>Cultured normal human umbilical cord vein endothelial cells (HUVECs) were treated with L-OHP or L-OHP + NSAID flurbiprofen for 2 h and analyzed for the release of PGE2 and 15d-PGJ2 into culture supernatant by ELISA.<bold>Results: </bold>The results showed that L-OHP significantly and dose-dependently increased PGE2 secretion by HUVECs; however, flurbiprofen effectively prevented PGE2 increase. On the other hand, cisplatin, another platinum anticancer drug, did not stimulate PGE2 production. Other PGs, including 15d-PGJ2, 6-keto PGF1α, PGF2α, and PGD2 were not increased by L-OHP or cisplatin. Protein expression analysis revealed that cyclooxygenase 1 and cytoplasmic PGE synthase involved in constitutive PG metabolism were expressed in HUVECs but not affected by L-OHP exposure.<bold>Conclusions: </bold>This study indicates that L-OHP treatment specifically upregulated PGE2 secretion by vascular endothelial cells, which may contribute to vascular pain, and that NSAIDs can be used to inhibit PGE2 release and attenuate L-OHP-induced hyperalgesia.
- Subjects
VASCULAR endothelial cells; DINOPROSTONE; OXALIPLATIN; ENDOTHELIUM; ANTI-inflammatory agents; ARACHIDONIC acid; THERAPEUTIC use of antineoplastic agents; CELL culture; ANTINEOPLASTIC agents; EPITHELIAL cells; PHARMACODYNAMICS
- Publication
Cancer Chemotherapy & Pharmacology, 2019, Vol 84, Issue 2, p345
- ISSN
0344-5704
- Publication type
journal article
- DOI
10.1007/s00280-019-03901-7