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Antisense oligodeoxynucleotide against human telomerase reverse transcriptase inhibits the proliferation of Eca-109 esophageal carcinoma cells.
[esophageal carcinoma]
Previous
studies
have
demonstrated
that
the
growth
of
tumor
cells
may
be
inhibited
by
antisense
oligonucleotides
(
ASODNs
)
targeted
against
human
telomerase
(
hTR
)
or
human
telomerase
reverse
transcriptase
(
hTERT
)
,
resulting
in
antitumor
activity
in
a
wide
variety
of
tumors
.
However
,
few
studies
have
investigated
the
effect
of
hTERT
gene
-targeted
ASODNs
on
telomerase
activity
and
cell
proliferation
in
human
esophageal
cancer
.
In
the
present
study
,
an
MTT
assay
was
used
to
determine
the
growth
inhibition
rate
of
Eca-
109
cells
treated
with
a
hTERT-targeted
phosphorothioate-
ASODN
(
PS-ASODN
)
.
An
inverted
microscope
was
used
to
observe
the
morphologic
changes
of
the
cells
following
treatment
with
5
μM
PS-ASODN
for
10
days
.
Telomerase
activity
was
detected
using
the
silver
staining
semi-quantitative
telomeric
repeat
amplification
protocol
(
TRAP
)
assay
.
Following
treatment
with
the
PS-ASODN
(
1
-
5
μmol
/
l
)
,
the
proliferation
of
the
Eca-
109
cells
was
inhibited
.
The
differences
in
inhibition
rate
between
the
PS-ASODN
and
blank
control
groups
were
statistically
significant
(
P
<
0
.
05
)
when
the
concentration
of
the
PS-ASODN
was
≥
2
μmol
/
l
,
whereas
no
statistically
significant
difference
was
identified
between
the
non-
specific
-
ASODN
and
blank
control
groups
.
The
inhibition
rate
increased
gradually
as
the
concentration
of
the
PS-ASODN
increased
and
with
time
,
suggesting
that
the
PS-ASODN
inhibited
the
growth
of
Eca-
109
cells
in
a
concentration-dependent
,
time-dependent
and
sequence-
specific
manner
.
The
growth
rate
of
the
cells
incubated
with
the
PS-ASODN
was
reduced
compared
with
that
of
the
control
cells
.
Cells
treated
with
the
PS-ASODN
became
round
,
suspended
and
reduced
in
size
.
The
PS-ASODN
was
also
found
to
inhibit
telomerase
activity
.
The
ability
of
the
PS-ASODN
to
inhibit
the
telomerase
activity
and
cell
proliferation
of
the
Eca-
109
cell
line
suggests
that
ASODNs
have
the
potential
to
be
novel
therapeutic
agents
for
the
treatment
of
esophageal
cancer
.
Diseases
Validation
Diseases presenting
"specific manner"
symptom
aromatase deficiency
esophageal adenocarcinoma
esophageal carcinoma
familial hypocalciuric hypercalcemia
gm1 gangliosidosis
holt-oram syndrome
werner syndrome
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