Artículo
Chloroquine plays a cell-dependent role in the response to treatment of pancreatic adenocarcinoma
Molejon, Maria Ines
; Swayden, Mirna; Fanale, Daniele; Bintz, Jennifer; Gayet, Odile; Soubeyran, Philippe; Iovanna, Juan Lucio
Fecha de publicación:
07/2018
Editorial:
Impact Journals
Revista:
Oncotarget
ISSN:
1949-2553
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
In this study, our aim is to assess the role played by autophagy and its inhibition in the different PDAC cellular compartments, and its involvement in chemo-resistance using primary human pancreatic cancer-derived cells (PCC) and Cancer Associated Fibroblasts (CAF). Autophagy flux, as measured by LC3-I and -II in the presence of Chloroquine, showed a variable level in PCC and CAFs. We found no correlation between autophagy level and degree of tumor differentiation. Association of Chloroquine with gemcitabine, 5FU, oxaliplatin, irinotecan and docetaxel revealed that its effect on survival is cell- and drug-dependent in vitro and in vivo. In addition, we demonstrated that autophagy in CAFs can play an important role in sensitizing PDAC to anticancer treatments since its inhibition increased the resistance of PCCs to gemcitabine. In conclusion, this work clearly shows a heterogeneity in the effect of Chloroquine and highlights a role of CAFs autophagy in sensitizing tumors to treatments. It also reveals that the role of autophagy is more complex than expected in PDAC as well as its sensitivity to treatments.
Palabras clave:
AUTOPHAGY
,
CHLOROQUINE
,
GEMCITABINE
,
PANCREAS CANCER
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Articulos(INCITAP)
Articulos de INST.D/CS D/L/TIERRA Y AMBIENTALES D/L/PAMPA
Articulos de INST.D/CS D/L/TIERRA Y AMBIENTALES D/L/PAMPA
Citación
Molejon, Maria Ines; Swayden, Mirna; Fanale, Daniele; Bintz, Jennifer; Gayet, Odile; et al.; Chloroquine plays a cell-dependent role in the response to treatment of pancreatic adenocarcinoma; Impact Journals; Oncotarget; 9; 56; 7-2018; 30837-30846
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