The effect of Captopril and Iosar tan on Angiogenesis of Rat Orthotopic Hepatocellular Carcinoma
Date Issued
2000-07-31
Date
2000-07-31
Author(s)
袁瑞晃
DOI
892314B002220
Abstract
The assessment of angiogenesis
provides a promising horizon in the
pathogenesis of a variety of cancer diseases.
Recent studies of angiogenesis demonstrated
an important role of angiogenesis in cancer
growth and metastasis. In the mean time,
inhibition of angiogenesis might provide a
new approach in cancer treatment. Reports
concerning angiogenesis of hepatocellular
carcinoma were restricted to either secretion
function of angiogenic factors in cell lines or
to histochemical studies on human
hepatocellular carcinoma tissue
retrospectively at present. Unfortunately, a
prospective study of anti-angiogenesis in an
orthotopic hepatocellular carcinoma in rat is not present.
Captopril is an inhibitor of angiotensin
converting enzyme, which can reduce the
production of angiotensin II, and is widely
used clinically in the management of
hypertesive disease. Inhibition of DNA
production in endothelial cells by captopril
resulted in decreasing of angiogenesis had
been reported recently. But further
researches are demanded to study the
mechanism. Iosartan, a new developed drug
for hypertension treatment, is an antagonist
of angiotensin II subtype I receptor with
competitive inhibition of angiotensin II. It's
worth to understand the effect of drug in
order to clarify the role of angiotensin II in
angiogenesis.
In this study, we use the chemical
carcinogen transformed hepatic epithelial
cancer cell line, GP7TB to establish an
orthotopic hepatocellular carcinoma model
for in vivo study. GP7TB cell suspension is
inoculated subcutaneous in the posterior
flanks of the rats. Two to three weeks later,
tumor formed at subcutaneous region will be
excised and cut into uniform fragments of
about 1 mm3. Then the fragment is
transplanted into the liver of syngeneic
Fischer 334 rats. The rats will be divided into
3 groups. In Control (C) group, only normal
saline was given, In Captopril (CA) group, 60
mg/kg/day of Captopril will be given. In
Iosartan (I) group, 20 mg/kg/day of Iosartan
will be given. After 14 and 21 days, the rats
will be sacrificed and the size, weight of the
tumor will be recorded. In addition,
quantification of angiogenic factors including
vascular epithelial growth factor, and basic
fibroblast growth factor as well as ability of
mRNA expression will be done at the same
time. The differences of anti-angiogenic
ability and mechanism between Captopril and
Iosartan will be discussed.
Subjects
Rat hepatocellular carcinoma
Angiogenesis
Vascular endothelial growth factor
Basic
fibroblast growth factor
fibroblast growth factor
microvessel density
SDGs
Publisher
臺北市：國立臺灣大學醫學院外科
Type
report
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