IDEHU   05542
INSTITUTO DE ESTUDIOS DE LA INMUNIDAD HUMORAL PROF. RICARDO A. MARGNI
Unidad Ejecutora - UE
artículos
Título:
Hyaluronan oligosaccharides sensitize lymphoid leukemic resistant cell lines to vincristine by modulating P-glycoprotein activity and PI3K/Akt pathway.
Autor/es:
CORDÓ RUSSO ROSALÍA; GARCIA MARIANA; ALANIZ LAURA; BLANCO GUILLERMO; ALVAREZ ELIDA; HAJOS SILVIA
Revista:
INTERNATIONAL JOURNAL OF CANCER. JOURNAL INTERNATIONAL DU CANCER.
Editorial:
Wiley Publisher
Referencias:
Lugar: Nueva Jersey- USA.; Año: 2007
ISSN:
0020-7136
Resumen:
Multidrug resistance (MDR) is one of the main reasons for failure
of cancer therapy. It may be mediated by overexpression of ATPdependent
efflux pumps or by alterations in survival or apoptotic
pathways. Fragments generated by enzymatic degradation of hyaluronan
(oHA) were able to modulate growth and cell survival
and sensitize MDR breast cancer cells to cytotoxic drugs. In this
work the relationship between oHA and MDR in lymphoid malignancies
was analyzed using murine lymphoma cell lines resistant
to doxorubicin (LBR-D160) or vincristine (LBR-V160) and a sensitive
line (LBR-). After oHA treatment, higher apoptosis levels
were observed in the resistant cell lines than in the sensitive one.
Besides, oHA sensitized LBR-D160 and LBR-V160 to vincristine
showing increased apoptosis induction when used in combination
with vincristine. Native hyaluronan failed to increase apoptosis
levels. As different survival factors could be modulated by hyaluronan,
we investigated the PI3K/Akt pathway through PIP3 production
and phosphorylated Akt (p-Akt) and survivin expression
was also evaluated. Our results showed that oHA decreased p-Akt
in the 3 cell lines while anti-CD44 treatment abolished this effect.
Besides, survivin was downregulated only in LBR-V160 by oHA.
When Pgp function was evaluated, we observed that oHA were
able to inhibit Pgp efflux in murine and human resistant cell lines
in a CD44-dependent way. In summary, we report for the first
time that oHA per se modulate MDR in lymphoma cells by
decreasing p-Akt as well as Pgp activity, thus suggesting that oHA
could be useful in combination with classical chemotherapy in
MDR hematological malignancies.
decreasing p-Akt as well as Pgp activity, thus suggesting that oHA
could be useful in combination with classical chemotherapy in
MDR hematological malignancies.
decreasing p-Akt as well as Pgp activity, thus suggesting that oHA
could be useful in combination with classical chemotherapy in
MDR hematological malignancies.
decreasing p-Akt as well as Pgp activity, thus suggesting that oHA
could be useful in combination with classical chemotherapy in
MDR hematological malignancies.
decreasing p-Akt as well as Pgp activity, thus suggesting that oHA
could be useful in combination with classical chemotherapy in
MDR hematological malignancies.
per se modulate MDR in lymphoma cells by
decreasing p-Akt as well as Pgp activity, thus suggesting that oHA
could be useful in combination with classical chemotherapy in
MDR hematological malignancies.
´ 2007 Wiley-Liss, Inc.2007 Wiley-Liss, Inc.