Oxaliplatin induces prostaglandin E2 release in vascular endothelial cells.

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) E and 15d-PGJ 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 PGE and 15d-PGJ into culture supernatant by ELISA.

Results: The results showed that L-OHP significantly and dose-dependently increased PGE secretion by HUVECs; however, flurbiprofen effectively prevented PGE increase. On the other hand, cisplatin, another platinum anticancer drug, did not stimulate PGE production. Other PGs, including 15d-PGJ, 6-keto PGF, PGF, and PGD 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 PGE secretion by vascular endothelial cells, which may contribute to vascular pain, and that NSAIDs can be used to inhibit PGE release and attenuate L-OHP-induced hyperalgesia.