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JAK2 inhibitor blocks the inflammation and growth of esophageal squamous cell carcinoma in vitro through the JAK/STAT3 pathway.
[esophageal squamous cell carcinoma]
Recent
research
indicates
that
the
Janus
kinase
/
signal
transducer
and
activator
of
transcription
Â
3
(
JAK
/
STAT
3
)
pathway
may
play
an
important
role
in
chronic
inflammation
which
promotes
cancer
progression
,
yet
the
mechanism
is
not
clear
.
The
present
study
aimed
to
investigate
the
role
of
the
JAK
/
STAT
3
pathway
in
the
growth
and
cancer
-related
inflammation
(
CRI
)
of
esophageal
squamous
cell
carcinoma
(
ESCC
)
by
studying
the
crosstalk
between
the
JAK
/
STAT
3
pathway
and
nuclear
factor
-κ
B
(
NF-κB
)
and
cyclooxygenase-
2
(
COX
-
2
)
which
are
important
inflammatory
factors
associated
with
tumorigenesis
.
Cell
growth
and
the
cell
cycle
were
assessed
by
CCK
-
8
assays
and
flow
cytometry
,
respectively
.
The
protein
levels
of
STAT
3
,
phosphorylated
STAT
3
,
VEGF
,
NF-κB
p
65
,
phosphorylated
NF-κB
p
65
and
COX
-
2
in
ESCC
cells
following
treatment
with
JAK
2
inhibitor
for
48
Â
h
or
interleukin-
6
(
IL
-
6
)
for
24
Â
h
were
detected
.
RT-PCR
was
performed
to
study
the
interaction
among
STAT
3
,
NF-κB
and
COX
-
2
by
transfection
of
siRNAs
targeted
at
STAT
3
and
NF-κB
.
STAT
3
was
activated
in
3
Â
ESCC
cell
lines
at
different
levels
.
Blocking
the
JAK
/
STAT
3
pathway
inhibited
cancer
growth
through
regulation
of
cell
growth
,
cell
cycle
and
angiogenesis
.
Likewise
,
abrogation
of
the
JAK
/
STAT
3
pathway
decreased
CRI
by
downregulating
levels
of
NF-κB
p
65
phosphorylation
,
COX
-
2
and
IL
-
6
concentration
.
In
addition
,
CRI
and
cancer
growth
were
accelerated
by
IL
-
6
through
stimulation
of
the
JAK
/
STAT
3
and
NF-κB
p
65
pathway
.
Moreover
,
STAT
3
and
NF-κB
both
regulated
COX
-
2
as
a
downstream
gene
.
The
JAK
/
STAT
3
pathway
is
an
important
pathway
which
links
CRI
and
cancer
growth
through
IL
-
6
and
crosstalk
with
the
NF-κB
p
65
subunit
and
COX
-
2
.
The
STAT
3
pathway
could
be
a
novel
target
both
for
cancer
treatment
and
prevention
in
ESCC
.
Diseases
Validation
Diseases presenting
"cancer-related"
symptom
cowden syndrome
cushing syndrome
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
neuralgic amyotrophy
primary effusion lymphoma
systemic capillary leak syndrome
thoracic outlet syndrome
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