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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
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
h
or
interleukin-
6
(
IL
-
6
)
for
24
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
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"
symptom
achondroplasia
acute rheumatic fever
adrenal incidentaloma
alpha-thalassemia
benign recurrent intrahepatic cholestasis
cadasil
canavan disease
carcinoma of the gallbladder
cholangiocarcinoma
coats disease
congenital adrenal hyperplasia
congenital diaphragmatic hernia
cowden syndrome
cushing syndrome
cutaneous mastocytosis
dedifferentiated liposarcoma
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
erdheim-chester disease
erythropoietic protoporphyria
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
familial hypocalciuric hypercalcemia
familial mediterranean fever
gm1 gangliosidosis
heparin-induced thrombocytopenia
hereditary cerebral hemorrhage with amyloidosis
hirschsprung disease
hodgkin lymphoma, classical
inclusion body myositis
junctional epidermolysis bullosa
kabuki syndrome
kallmann syndrome
kindler syndrome
lamellar ichthyosis
liposarcoma
locked-in syndrome
lymphangioleiomyomatosis
monosomy 21
neuralgic amyotrophy
oculocutaneous albinism
oligodontia
oral submucous fibrosis
papillon-lefèvre syndrome
pendred syndrome
pleomorphic liposarcoma
primary effusion lymphoma
proteus syndrome
pyomyositis
pyruvate dehydrogenase deficiency
severe combined immunodeficiency
sneddon syndrome
systemic capillary leak syndrome
triple a syndrome
von hippel-lindau disease
waldenström macroglobulinemia
well-differentiated liposarcoma
werner syndrome
wiskott-aldrich syndrome
wolf-hirschhorn syndrome
x-linked adrenoleukodystrophy
This symptom has already been validated