Growth Hormone Receptor Antagonist Markedly Improves Gemcitabine Response in a Mouse Xenograft Model of Human Pancreatic Cancer
Published: May 13, 2024
Chemotherapy
treatment
against
pancreatic
ductal
adenocarcinoma
(PDAC)
is
thwarted
by
tumoral
activation
of
multiple
therapy-resistance
pathways.
The
growth
hormone
(GH)
–
GH
receptor
(GHR)
pair
a
covert
driver
multimodal
therapy
resistance
in
cancer,
and
overexpressed
PDAC
tumors,
yet
the
therapeutic
potential
targeting
same
has
not
been
explored.
Here,
we
report
that
GHR
expression
negative
prognostic
factor
patients
with
PDAC.
Combinations
gemcitabine
different
antagonists
(GHRAs)
markedly
improve
outcomes
nude
mice
xenografts.
Employing
cultured
cells,
mouse
xenografts,
analyses
human
transcriptome,
identified
attenuation
multidrug
transporter
epithelial-to-mesenchymal
transition
programs
tumors
underlie
observed
augmentation
chemotherapy
efficacy
GHRAs.
Moreover,
patients,
strongly
correlates
gene
signature
tumor-promotion
immune-evasion,
which
corroborate
syngeneic
wild-type
vs.
transgenic
mice.
Overall,
found
action
promoted
therapy-refractory
vivo,
can
be
effectively
attenuated
antagonism.
Our
results
collectively
present
proof
concept
towards
considering
antagonist
to
chemotherapeutic
outcome
highly
chemoresistant
Language: Английский
Growth Hormone Upregulates Melanoma Drug Resistance and Migration via Melanoma Derived Exosomes
Published: July 1, 2024
Drug
resistance
in
melanoma
is
a
major
hindrance
cancer
therapy.
Growth
hormone
(GH)
plays
pivotal
role
contributing
to
chemotherapy.
Knocking
down
or
blocking
the
GH
receptor
has
been
shown
sensitize
tumor
cells
Extensive
studies
have
demonstrated
that
exosomes,
subset
of
extracellular
vesicles,
play
an
important
drug
by
transferring
key
factors
In
this
study,
we
explore
how
modulates
exosomal
cargoes
from
and
their
resistance.
We
treated
with
GH,
doxorubicin,
GHR
antagonist,
pegvisomant,
analyzed
exosomes
released.
Additionally,
administered
these
recipient
cells.
The
GH-treated
released
elevated
levels
ABC
transporters
(ABCC1
ABCB1),
N-cadherin
MMP2,
enhancing
migration
antagonism
reduced
levels,
restoring
sensitivity
attenuating
migration.
Overall,
our
findings
highlight
novel
modulating
drive
chemoresistance
metastasis
melanoma.
This
understanding
provides
insights
mechanisms
suggests
as
potential
therapy
overcome
treatment.
Language: Английский
Growth Hormone Upregulates Melanoma Drug Resistance and Migration via Melanoma-Derived Exosomes
Cancers,
Journal Year:
2024,
Volume and Issue:
16(15), P. 2636 - 2636
Published: July 24, 2024
Drug
resistance
in
melanoma
is
a
major
hindrance
cancer
therapy.
Growth
hormone
(GH)
plays
pivotal
role
contributing
to
the
chemotherapy.
Knocking
down
or
blocking
GH
receptor
has
been
shown
sensitize
tumor
cells
Extensive
studies
have
demonstrated
that
exosomes,
subset
of
extracellular
vesicles,
play
an
important
drug
by
transferring
key
factors
In
this
study,
we
explore
how
modulates
exosomal
cargoes
from
and
their
resistance.
We
treated
with
GH,
doxorubicin,
GHR
antagonist,
pegvisomant,
analyzed
exosomes
released.
Additionally,
administered
these
recipient
cells.
The
GH-treated
released
elevated
levels
ABC
transporters
(ABCC1
ABCB1),
N-cadherin,
MMP2,
enhancing
migration
antagonism
reduced
levels,
restoring
sensitivity
attenuating
migration.
Overall,
our
findings
highlight
novel
modulating
drive
chemoresistance
metastasis
melanoma.
This
understanding
provides
insights
into
mechanisms
suggests
as
potential
therapy
overcome
treatment.
Language: Английский