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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
"wide variety"
symptom
alexander disease
allergic bronchopulmonary aspergillosis
cadasil
erythropoietic protoporphyria
esophageal carcinoma
familial hypocalciuric hypercalcemia
gm1 gangliosidosis
junctional epidermolysis bullosa
lamellar ichthyosis
lymphangioleiomyomatosis
oral submucous fibrosis
pleomorphic liposarcoma
proteus syndrome
severe combined immunodeficiency
x-linked adrenoleukodystrophy
zellweger syndrome
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