Endothelin-A receptor in gastric cancer and enhanced antitumor activity of trastuzumab in combination with the endothelin-A receptor antagonist ZD4054.
Adult
Aged
Aged, 80 and over
Animals
Antineoplastic Agents, Immunological
/ pharmacology
Antineoplastic Combined Chemotherapy Protocols
/ pharmacology
Apoptosis
/ drug effects
Cell Line, Tumor
Cell Proliferation
/ drug effects
Drug Synergism
Endothelin A Receptor Antagonists
/ pharmacology
ErbB Receptors
/ metabolism
Female
Gastric Mucosa
/ pathology
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Middle Aged
Pyrrolidines
/ pharmacology
Receptor, Endothelin A
/ genetics
Stomach Neoplasms
/ drug therapy
Trastuzumab
/ pharmacology
Xenograft Model Antitumor Assays
combinatorial therapy
endothelin-A receptor
gastric cancer
prognosis
Journal
Annals of the New York Academy of Sciences
ISSN: 1749-6632
Titre abrégé: Ann N Y Acad Sci
Pays: United States
ID NLM: 7506858
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
23
10
2018
revised:
30
11
2018
accepted:
21
02
2019
pubmed:
3
4
2019
medline:
9
4
2020
entrez:
3
4
2019
Statut:
ppublish
Résumé
Endothelin-A receptor (ETAR) is overexpressed in cancers and can function through transactivation of the epidermal growth factor receptor. We explored ETAR in gastric cancer and investigated the antitumor effect of trastuzumab in combination with the ETAR antagonist ZD4054. The expression of ETAR was significantly correlated with the expression of vascular endothelial growth factor. Univariate and multivariate analyses further showed that ETAR expression correlated with reduced survival in gastric cancer patients. In vitro, ZD4054 increased the antiproliferative effect of trastuzumab in gastric cancer cell lines. Moreover, the addition of ZD4054 to trastuzumab significantly increased apoptosis in gastric cancer cell lines. In vivo, tumor growth was considerably inhibited by treatment with ZD4054 and trastuzumab, and the tumor volume in the trastuzumab and ZD4054 combination group was smaller than in the other groups. The detection of ETAR could help predict the prognosis of gastric cancer patients. Additionally, this study provides support for the therapeutic use of the combination of ZD4054 and trastuzumab as an anticancer treatment, especially for gastric cancer.
Substances chimiques
Antineoplastic Agents, Immunological
0
Endothelin A Receptor Antagonists
0
Pyrrolidines
0
Receptor, Endothelin A
0
ZD4054
0
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Trastuzumab
P188ANX8CK
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
30-41Subventions
Organisme : National Nature Science Foundation of China
ID : 81272698
Pays : International
Informations de copyright
© 2019 New York Academy of Sciences.