Growth suppression of human oral cancer cells by candidate agents for cetuximab-side effects.
Animals
Antineoplastic Agents, Immunological
/ adverse effects
Carcinoma, Squamous Cell
/ complications
Cell Line, Tumor
Cetuximab
/ adverse effects
Drug Therapy, Combination
ErbB Receptors
/ antagonists & inhibitors
Exanthema
/ chemically induced
Female
Gene Expression Regulation, Neoplastic
/ drug effects
Gene Regulatory Networks
Growth Inhibitors
/ adverse effects
HEK293 Cells
Humans
Hypercalciuria
/ chemically induced
Imidazoles
/ therapeutic use
MAP Kinase Signaling System
/ drug effects
Mice
Mice, Inbred BALB C
Mice, Nude
Mouth Neoplasms
/ complications
Nephrocalcinosis
/ chemically induced
Pyridines
/ therapeutic use
Renal Tubular Transport, Inborn Errors
/ chemically induced
Transcriptome
Xenograft Model Antitumor Assays
Cetuximab side effects
Flavagline
SB203580
TRPM6
Tumor growth suppression
p38
Journal
Experimental cell research
ISSN: 1090-2422
Titre abrégé: Exp Cell Res
Pays: United States
ID NLM: 0373226
Informations de publication
Date de publication:
15 03 2019
15 03 2019
Historique:
received:
23
10
2018
revised:
15
01
2019
accepted:
24
01
2019
pubmed:
29
1
2019
medline:
27
5
2020
entrez:
29
1
2019
Statut:
ppublish
Résumé
Cetuximab, an inhibitor of the epidermal growth factor receptor that is used widely to treat human cancers including oral squamous cell carcinoma (OSCC), has characteristic side effects of skin rash and hypomagnesemia. However, the mechanisms of and therapeutic agents for skin rashes and hypomagnesemia are still poorly understood. Our gene expression profiling analyses showed that cetuximab activates the p38 MAPK pathways in human skin cells (human keratinocyte cell line [HaCaT]) and inhibits c-Fos-related signals in human embryonic kidney cells (HEK293). We found that while the p38 inhibitor SB203580 inhibited the expression of p38 MAPK targets in HaCaT cells, flavagline reactivated c-Fos-related factors in HEK293 cells. It is noteworthy that, in addition to not interfering with the effect of cetuximab by both compounds, flavagline has additive effect for OSCC growth inhibition in vivo. Collectively, our results indicate that combination of cetuximab and these potential therapeutic agents for cetuximab-related toxicities could be a promising therapeutic strategy for patients with OSCC.
Identifiants
pubmed: 30690028
pii: S0014-4827(19)30021-7
doi: 10.1016/j.yexcr.2019.01.016
pii:
doi:
Substances chimiques
Antineoplastic Agents, Immunological
0
Growth Inhibitors
0
Imidazoles
0
Pyridines
0
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
SB 203580
OU13V1EYWQ
Cetuximab
PQX0D8J21J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
210-220Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.