INVESTIGADORES
ALANIZ Laura Daniela
congresos y reuniones científicas
Título:
PI3K/Akt inhibition modulates multidrug resistance (MDR) and activates NF-ÛB in murine lymphoma cell lines
Autor/es:
GARCÍA MARIANA G; ALANIZ LAURA D; CORDO RUSSO R; ALVAREZ ELIDA; HAJOS SILVIA E
Lugar:
Rio de Janeiro, Brazil,
Reunión:
Congreso; 13th International Congress of Immunology; 2007
Institución organizadora:
Brazilian Society of Immunology (SBI)
Resumen:
Cellular responses toward cytotoxic drugs are controlled by cross-talk between oncogenic
signaling pathways and resistance mechanisms. The aim of this work was to analyze the
relationship between PI3K/Akt survival pathway and multidrug resistance (MDR) in murine
lymphoma resistant cell lines to vincristine (LBR-V160), doxorubicin (LBR-D160) and sensitive
line (LBR-). Higher PI3K/Akt activity was found in LBR-V160 and LBR-D160 compared to LBR-,
analyzed through phosphatidylinositol-trisphosphate production by TLC and phosphorylated Akt
(p-Akt) expression by western blot. Improved apoptosis was observed in LBR-D160
(17.7%±9.4% and 25.2%±7.3%) and LBR-V160 (17.4%±4.8% and 13.0%±5.6%) compared to
LBR- (3.7%±3.4% and 4.0%±1.8%) after PI3K inhibition with wortmannin or LY294002
respectively (P<0.01 vs LBR-), evaluated by Annexin V and acridine orange-ethidium bromide
staining. Both inhibitors also down-regulated survivin expression in the three cell lines while IB
phosphorylation was increased leading to down-regulation of IB expression. Higher NF-B
activity was also observed by EMSA assay after PI3K inhibition. Vincristine (VCR) but not
doxorubicin increased p-Akt expression while co-treatment with PI3K inhibitors and VCR
increased apoptosis in the three cell lines. After wortmannin or LY294002 treatment, Pglycoprotein
(Pgp) function was evaluated by flow cytometry showing a blockage of Pgp efflux
in resistant cell lines. We conclude that PI3K/Akt pathway is involved in MDR in these
lymphoma cell lines. Besides, PI3K inhibition correlates with apoptosis induction, survivin downregulation
and NF-B activation. PI3K inhibitors, wortmannin and LY294002, modulate MDR by
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
activity was also observed by EMSA assay after PI3K inhibition. Vincristine (VCR) but not
doxorubicin increased p-Akt expression while co-treatment with PI3K inhibitors and VCR
increased apoptosis in the three cell lines. After wortmannin or LY294002 treatment, Pglycoprotein
(Pgp) function was evaluated by flow cytometry showing a blockage of Pgp efflux
in resistant cell lines. We conclude that PI3K/Akt pathway is involved in MDR in these
lymphoma cell lines. Besides, PI3K inhibition correlates with apoptosis induction, survivin downregulation
and NF-B activation. PI3K inhibitors, wortmannin and LY294002, modulate MDR by
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
activity was also observed by EMSA assay after PI3K inhibition. Vincristine (VCR) but not
doxorubicin increased p-Akt expression while co-treatment with PI3K inhibitors and VCR
increased apoptosis in the three cell lines. After wortmannin or LY294002 treatment, Pglycoprotein
(Pgp) function was evaluated by flow cytometry showing a blockage of Pgp efflux
in resistant cell lines. We conclude that PI3K/Akt pathway is involved in MDR in these
lymphoma cell lines. Besides, PI3K inhibition correlates with apoptosis induction, survivin downregulation
and NF-B activation. PI3K inhibitors, wortmannin and LY294002, modulate MDR by
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
phosphorylation was increased leading to down-regulation of IB expression. Higher NF-B
activity was also observed by EMSA assay after PI3K inhibition. Vincristine (VCR) but not
doxorubicin increased p-Akt expression while co-treatment with PI3K inhibitors and VCR
increased apoptosis in the three cell lines. After wortmannin or LY294002 treatment, Pglycoprotein
(Pgp) function was evaluated by flow cytometry showing a blockage of Pgp efflux
in resistant cell lines. We conclude that PI3K/Akt pathway is involved in MDR in these
lymphoma cell lines. Besides, PI3K inhibition correlates with apoptosis induction, survivin downregulation
and NF-B activation. PI3K inhibitors, wortmannin and LY294002, modulate MDR by
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
activity was also observed by EMSA assay after PI3K inhibition. Vincristine (VCR) but not
doxorubicin increased p-Akt expression while co-treatment with PI3K inhibitors and VCR
increased apoptosis in the three cell lines. After wortmannin or LY294002 treatment, Pglycoprotein
(Pgp) function was evaluated by flow cytometry showing a blockage of Pgp efflux
in resistant cell lines. We conclude that PI3K/Akt pathway is involved in MDR in these
lymphoma cell lines. Besides, PI3K inhibition correlates with apoptosis induction, survivin downregulation
and NF-B activation. PI3K inhibitors, wortmannin and LY294002, modulate MDR by
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
activity was also observed by EMSA assay after PI3K inhibition. Vincristine (VCR) but not
doxorubicin increased p-Akt expression while co-treatment with PI3K inhibitors and VCR
increased apoptosis in the three cell lines. After wortmannin or LY294002 treatment, Pglycoprotein
(Pgp) function was evaluated by flow cytometry showing a blockage of Pgp efflux
in resistant cell lines. We conclude that PI3K/Akt pathway is involved in MDR in these
lymphoma cell lines. Besides, PI3K inhibition correlates with apoptosis induction, survivin downregulation
and NF-B activation. PI3K inhibitors, wortmannin and LY294002, modulate MDR by
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
phosphorylation was increased leading to down-regulation of IB expression. Higher NF-B
activity was also observed by EMSA assay after PI3K inhibition. Vincristine (VCR) but not
doxorubicin increased p-Akt expression while co-treatment with PI3K inhibitors and VCR
increased apoptosis in the three cell lines. After wortmannin or LY294002 treatment, Pglycoprotein
(Pgp) function was evaluated by flow cytometry showing a blockage of Pgp efflux
in resistant cell lines. We conclude that PI3K/Akt pathway is involved in MDR in these
lymphoma cell lines. Besides, PI3K inhibition correlates with apoptosis induction, survivin downregulation
and NF-B activation. PI3K inhibitors, wortmannin and LY294002, modulate MDR by
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
activity was also observed by EMSA assay after PI3K inhibition. Vincristine (VCR) but not
doxorubicin increased p-Akt expression while co-treatment with PI3K inhibitors and VCR
increased apoptosis in the three cell lines. After wortmannin or LY294002 treatment, Pglycoprotein
(Pgp) function was evaluated by flow cytometry showing a blockage of Pgp efflux
in resistant cell lines. We conclude that PI3K/Akt pathway is involved in MDR in these
lymphoma cell lines. Besides, PI3K inhibition correlates with apoptosis induction, survivin downregulation
and NF-B activation. PI3K inhibitors, wortmannin and LY294002, modulate MDR by
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
activity was also observed by EMSA assay after PI3K inhibition. Vincristine (VCR) but not
doxorubicin increased p-Akt expression while co-treatment with PI3K inhibitors and VCR
increased apoptosis in the three cell lines. After wortmannin or LY294002 treatment, Pglycoprotein
(Pgp) function was evaluated by flow cytometry showing a blockage of Pgp efflux
in resistant cell lines. We conclude that PI3K/Akt pathway is involved in MDR in these
lymphoma cell lines. Besides, PI3K inhibition correlates with apoptosis induction, survivin downregulation
and NF-B activation. PI3K inhibitors, wortmannin and LY294002, modulate MDR by
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
B
phosphorylation was increased leading to down-regulation of IB expression. Higher NF-B
activity was also observed by EMSA assay after PI3K inhibition. Vincristine (VCR) but not
doxorubicin increased p-Akt expression while co-treatment with PI3K inhibitors and VCR
increased apoptosis in the three cell lines. After wortmannin or LY294002 treatment, Pglycoprotein
(Pgp) function was evaluated by flow cytometry showing a blockage of Pgp efflux
in resistant cell lines. We conclude that PI3K/Akt pathway is involved in MDR in these
lymphoma cell lines. Besides, PI3K inhibition correlates with apoptosis induction, survivin downregulation
and NF-B activation. PI3K inhibitors, wortmannin and LY294002, modulate MDR by
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
activity was also observed by EMSA assay after PI3K inhibition. Vincristine (VCR) but not
doxorubicin increased p-Akt expression while co-treatment with PI3K inhibitors and VCR
increased apoptosis in the three cell lines. After wortmannin or LY294002 treatment, Pglycoprotein
(Pgp) function was evaluated by flow cytometry showing a blockage of Pgp efflux
in resistant cell lines. We conclude that PI3K/Akt pathway is involved in MDR in these
lymphoma cell lines. Besides, PI3K inhibition correlates with apoptosis induction, survivin downregulation
and NF-B activation. PI3K inhibitors, wortmannin and LY294002, modulate MDR by
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
activity was also observed by EMSA assay after PI3K inhibition. Vincristine (VCR) but not
doxorubicin increased p-Akt expression while co-treatment with PI3K inhibitors and VCR
increased apoptosis in the three cell lines. After wortmannin or LY294002 treatment, Pglycoprotein
(Pgp) function was evaluated by flow cytometry showing a blockage of Pgp efflux
in resistant cell lines. We conclude that PI3K/Akt pathway is involved in MDR in these
lymphoma cell lines. Besides, PI3K inhibition correlates with apoptosis induction, survivin downregulation
and NF-B activation. PI3K inhibitors, wortmannin and LY294002, modulate MDR by
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
B expression. Higher NF-B
activity was also observed by EMSA assay after PI3K inhibition. Vincristine (VCR) but not
doxorubicin increased p-Akt expression while co-treatment with PI3K inhibitors and VCR
increased apoptosis in the three cell lines. After wortmannin or LY294002 treatment, Pglycoprotein
(Pgp) function was evaluated by flow cytometry showing a blockage of Pgp efflux
in resistant cell lines. We conclude that PI3K/Akt pathway is involved in MDR in these
lymphoma cell lines. Besides, PI3K inhibition correlates with apoptosis induction, survivin downregulation
and NF-B activation. PI3K inhibitors, wortmannin and LY294002, modulate MDR by
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.
B activation. PI3K inhibitors, wortmannin and LY294002, modulate MDR by
both PI3K/Akt and Pgp function inhibition. Therefore, PI3K/Akt signaling cascade may be
considered as an attractive target for therapeutic intervention.