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Amiloride and guggulsterone suppression of esophageal cancer cell growth in vitro and in nude mouse xenografts.
[esophageal adenocarcinoma]
Esophageal
adenocarcinoma
is
increasing
in
the
US
and
Western
countries
and
frequent
gastresophageal
reflux
or
gastresophageal
reflux
disease
carrying
gastric
acid
and
bile
acid
could
contribute
to
esophageal
adenocarcinogenesis
.
This
study
was
designed
to
detect
the
expression
of
gastric
acid-inducing
gene
Na
+
/
H
+
exchanger-
1
(
NHE-
1
)
ex
vivo
and
then
to
explore
targeting
of
NHE-
1
expression
or
activity
to
control
esophageal
cancer
cell
viability
in
vitro
and
in
nude
mouse
xenografts
.
The
data
showed
that
NHE-
1
was
highly
expressed
in
esophageal
adenocarcinoma
tissues
(
66
of
101
cases
[
65
.
3
%
]
,
but
not
in
normal
esophageal
squamous
cell
epithelium
(
1
of
26
cases
[
3
.
8
%
]
)
.
Knockdown
of
NHE-
1
expression
using
NHE-
1
shRNA
or
inhibition
of
NHE-
1
activity
using
the
NHE-
1
inhibitor
amiloride
suppressed
viability
and
induced
apoptosis
in
esophageal
cancer
cells
.
Molecularly
,
amiloride
inhibited
expression
of
cyclooxygenase-
2
and
matrix
metallopeptidase-
9
but
not
NHE-
1
mRNA
in
esophageal
cancer
cells
.
A
combination
of
amiloride
and
guggulsterone
(
a
natural
bile
acid
receptor
inhibitor
)
showed
more
than
additive
effects
in
suppressing
esophageal
cancer
cell
growth
in
vitro
and
in
nude
mouse
xenografts
.
This
study
suggests
that
inhibition
of
NHE-
1
expression
or
activity
or
combination
of
amiloride
and
guggulsterone
could
be
useful
in
control
of
esophageal
adenocarcinoma
.