Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 2/2019

01-08-2019 | Original Article

Oxaliplatin induces prostaglandin E2 release in vascular endothelial cells

Authors: Satoru Matsunuma, Satoko Handa, Daisuke Kamei, Hitomi Yamamoto, Kiyoshi Okuyama, Yasuhisa Kato

Published in: Cancer Chemotherapy and Pharmacology | Issue 2/2019

Login to get access

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.
Literature
1.
Cassidy J, Clarke S, Díaz-Rubio E et al (2008) Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol 26:2006–2012CrossRefPubMed
2.
Yamada Y, Takahari D, Matsumoto H et al (2013) Leucovorin, fluorouracil, and oxaliplatin plus bevacizumab versus S-1 and oxaliplatin plus bevacizumab in patients with metastatic colorectal cancer (SOFT): an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol 14:1278–1286CrossRefPubMed
3.
Fuse N, Bando H, Chin K et al (2017) Adjuvant capecitabine plus oxaliplatin after D2 gastrectomy in Japanese patients with gastric cancer: a phase II study. Gastric Cancer 20:332–340CrossRefPubMed
4.
Suga Y, Sakaguchi Y, Ishizaki J et al (2012) Investigation for risk factor and preventive effect of NSAIDs, opioid on gemcitabine-induced vascular pain. Jpn J Pharm Heal Care Sci 38:177–183CrossRef
5.
Yoh K, Niho S, Goto K (2004) High body mass index correlates with increased risk of venous irritation by vinorelbine infusion. Jpn J Clin Oncol 34:206–209CrossRefPubMed
6.
Kawahara M, Ishida T, Emoto C et al (2001) Determination of a pain substance produced by the photodegradation of dacarbazine. Jpn J Clin Pharmacol Ther 32:15–22CrossRef
7.
Suga Y, Kumazaki M, Nishigami J et al (2009) Improvement of epirubicin-induced phlebitis to switch from liquid preparation to lyophilized formulation. Gan Kagaku Ryoho 36:93–96
8.
Hino M, Haruta K, Yoshimura T et al (2008) Evaluation and measurement of vascular pain developing during administration of gemcitabine hydrochloride. J Jpn Soc Hosp Pharm 44:801–803
9.
Yoh K, Niho S, Goto K et al (2007) Randomized trial of drip infusion versus bolus injection of vinorelbine for the control of local venous toxicity. Lung Cancer 55:337–341CrossRefPubMed
10.
Onogawa M, Ogawa K, Miyamura M (2010) Improvement of injection procedure for epirubicin hydrochloride to reduce venous pain. Jpn J Clin Pharmacol Ther 36:680–683
11.
Morio K, Tsugane M, Okamoto Y et al (2013) Effectiveness of a newly designed shield to prevent the photodegradation of dacarbazine. Jpn J Clin Pharmacol Ther 39:381–387
12.
Handa S, Kuroiwa R, Miyano M et al (2016) Assessment of injection site reactions for peripheral intravenous oxaliplatin infusion and potential remedies. Gan Kagaku Ryoho 43:985–988
13.
Lapeyre-Prost A, Hug de Larauze MH, Chibaudel B et al (2016) Feasibility of capecitabine and oxaliplatin combination chemotherapy without central venous access device in patients with stage III colorectal cancer. Clin Colorectal Cancer 15:250–256CrossRefPubMed
14.
15.
Kawaguchi H, Pilbeam CC, Harrison JR et al (1995) The role of prostaglandins in the regulation of bone metabolism. Clin Orthop Relat Res 313:36–46
16.
17.
Wallace JL (2008) Prostaglandins, NSAIDs, and gastric mucosal protection: why doesn’t the stomach digest itself? Physiol Rev 88:1547–1565CrossRefPubMed
18.
Murakami M, Naraba H, Tanioka T et al (2000) Regulation of prostaglandin E2 biosynthesis by inducible membrane-associated prostaglandin E2 synthase that acts in concert with cyclooxygenase-2. J Biol Chem 275:32783–32792CrossRefPubMed
19.
Murakami M, Nakashima K, Kamei D et al (2003) Cellular prostaglandin E2 production by membrane-bound prostaglandin E synthase-2 via both cyclooxygenases-1 and -2. J Biol Chem 278:37937–37947CrossRefPubMed
20.
21.
Kamei D, Yamakawa K, Takegoshi Y et al (2004) Reduced pain hypersensitivity and inflammation in mice lacking microsomal prostaglandin E synthase-1. J Biol Chem 279:33684–33695CrossRefPubMed
22.
Zhao M, Isami K, Nakamura S, Shirakawa H, Nakagawa T, Kaneko S (2012) Acute cold hypersensitivity characteristically induced by oxaliplatin is caused by the enhanced responsiveness of TRPA1 in mice. Mol Pain 8:55PubMedPubMedCentral
23.
Taylor-Clark TE, Undem BJ, Macglashan DW, Ghatta S, Carr MJ, McAlexander MA (2008) Prostaglandin-induced activation of nociceptive neurons via direct interaction with transient receptor potential A1 (TRPA1). Mol Pharmacol 73:274–281CrossRefPubMed
24.
Ferreira SH, Moncada S, Vane JR (1997) Prostaglandins and the mechanism of analgesia produced by aspirin-like drugs. Br J Pharmacol 120(1973):401–412 (discussion 399–400) CrossRefPubMedPubMedCentral
25.
Taiwo YO, Levine JD (1989) Prostaglandin effects after elimination of indirect hyperalgesic mechanisms in the skin of the rat. Brain Res 492:397–399CrossRefPubMed
26.
Narumiya S, Sugimoto Y, Ushikubi F (1999) Prostanoid receptors: structures, properties, and functions. Physiol Rev 79:1193–1226CrossRefPubMed
27.
Ando R, Watanabe C (2005) Characteristics of propofol-evoked vascular pain in anaesthetized rats. Br J Anaesth 95:384–392CrossRefPubMed
28.
Simmons DL, Botting RM, Hla T (2004) Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacol Rev 56:387–437CrossRefPubMed
29.
Tanioka T, Nakatani Y, Semmyo N, Murakami M, Kudo I (2000) Molecular identification of cytosolic prostaglandin E2 synthase that is functionally coupled with cyclooxygenase-1 in immediate prostaglandin E2 biosynthesis. J Biol Chem 275:32775–32782CrossRefPubMed
Metadata
Title
Oxaliplatin induces prostaglandin E2 release in vascular endothelial cells
Authors
Satoru Matsunuma
Satoko Handa
Daisuke Kamei
Hitomi Yamamoto
Kiyoshi Okuyama
Yasuhisa Kato
Publication date
01-08-2019
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 2/2019
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-019-03901-7

Other articles of this Issue 2/2019

Cancer Chemotherapy and Pharmacology 2/2019 Go to the issue

Original Article

Priming with GM-CSF instead of G-CSF enhances CAG-induced apoptosis of acute monocytic leukemia cells in vitro

Original Article

Neoadjuvant chemotherapy in patients with advanced endometrial cancer

Short Communication

CNS penetration of the CDK4/6 inhibitor ribociclib in non-tumor bearing mice and mice bearing pediatric brain tumors

Original Article

Phase I study of BGT226, a pan-PI3K and mTOR inhibitor, in Japanese patients with advanced solid cancers

Original Article

Effect of ethnicity on vinorelbine pharmacokinetics: a population pharmacokinetics analysis

Review Article

Cancer immunotherapy: the art of targeting the tumor immune microenvironment
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits