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ID 114596
Author
Kawasaki, Hiromu Matsuyama University
Fukuhara, Satoko Okayama University
Hashikawa-Hobara, Narumi Okayama University
Takatori, Shingo Matsuyama University
Keywords
Nerve growth factor
Tumor growth inhibition
HT1080 fibrosarcoma cell
HepG2 hepatitis cell
Perivascular innervation
Content Type
Journal Article
Description
This study investigated whether NGF prevents tumor growth by promoting neuronal regulation of tumor blood flow. HT1080 fibrosarcoma cells or HepG2 hepatitis cells were subcutaneously implanted into nude mice. On Day 21 after the implantation of tumor cells, human NGF (40 or 80 ng/h for 14 days) was administered using a micro-osmotic pump. Growth rates of both tumors were significantly inhibited by the treatment of NGF, and the survival rate was also extended. Significant suppression of HT1080 tumor growth lasted after withdrawing NGF. NGF markedly increased the density of α-smooth muscle actin (α-SMA)-immunoreactive (ir) cells without changing neovessel density in HT1080 tumor tissues. Double immunostaining demonstrated protein gene product (PGP) 9.5-ir nerves around α-SMA-ir cells were found in HT1080 tumor tissue treated with NGF. The blood flow in HepG2 tumors treated with saline was significantly higher than in the non-tumor control area, but the tumor blood flow was markedly reduced by NGF treatment. In in vitro studies, NGF significantly accelerated migration of aortic smooth muscle cells but not endothelial cells, whereas NGF had no cytotoxic action on both cells. NGF inhibits tumor growth via indirect action, probably through innervation and maturation of tumor neovasculature, which regulates blood flow into tumor tissues.
Journal Title
Journal of Pharmacological Sciences
ISSN
13478613
Publisher
Elsevier|Japanese Pharmacological Society
Volume
140
Issue
1
Start Page
1
End Page
7
Published Date
2019-05-23
Rights
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
University Hospital
Medical Sciences