Oxaliplatin induces prostaglandin E2 release in vascular endothelial cells.
Cancer Chemother Pharmacol
; 84(2): 345-350, 2019 08.
Article
em En
| MEDLINE
| ID: mdl-31243527
ABSTRACT
PURPOSE:
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.METHODS:
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.RESULTS:
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.CONCLUSIONS:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dinoprostona
/
Células Endoteliais
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Oxaliplatina
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Ano de publicação:
2019
Tipo de documento:
Article