RT Journal Article
T1 The Antitumor Activity of Sodium Selenite Alone and in Combination with Gemcitabine in Pancreatic Cancer: An In Vitro and In Vivo Study
A1 Doello, Kevin
A1 Mesas, Cristina
A1 Quiñonero, Francisco
A1 Perazzoli, Gloria
A1 Cabeza, Laura
A1 Prados, Jose
A1 Melguizo, Consolacion
A1 Ortiz, Raul
K1 Sodium selenite
K1 Gemcitabine
K1 Pancreatic cancer
K1 Cancer stem cells
K1 Combined therapy
K1 Phospho-p38 protein
K1 Selenito de sodio
K1 Antineoplásicos
K1 Neoplasias pancreáticas
K1 Células madre neoplásicas
K1 Tratamiento combinado
K1 Anticuerpos
AB Sodium selenite acts by depleting enzymes that protect against cellular oxidative stress. To determine its effect alone or in combination with gemcitabine (GMZ) in pancreatic cancer, we used PANC-1 and Pan02 cell lines and C57BL mice bearing a Pan02-generated tumor. Our results demonstrated a significant inhibition of pancreatic cancer cell viability with the use of sodium selenite alone and a synergistic effect when associated with GMZ. The molecular mechanisms of the antitumor effect of sodium selenite alone involved apoptosis-inducing factor (AIF) and the expression of phospho-p38 in the combined therapy. In addition, sodium selenite alone and in association with GMZ significantly decreased the migration capacity and colony-forming ability, reduced tumor activity in multicellular tumor spheroids (MTS) and decreased sphere formation of cancer stem cells. In vivo studies demonstrated that combined therapy not only inhibited tumor growth (65%) compared to the untreated group but also relative to sodium selenite or GMZ used as monotherapy (up to 40%), increasing mice survival. These results were supported by the analysis of C57BL/6 albino mice bearing a Pan02-generated tumor, using the IVIS system. In conclusion, our results showed that sodium selenite is a potential agent for the improvement in the treatment of pancreatic cancer and should be considered for future human clinical trials.
PB MDPI
YR 2021
FD 2021-06-25
LK http://hdl.handle.net/10668/4218
UL http://hdl.handle.net/10668/4218
LA en
NO Doello K, Mesas C, Quiñonero F, Perazzoli G, Cabeza L, Prados J, et al. The Antitumor Activity of Sodium Selenite Alone and in Combination with Gemcitabine in Pancreatic Cancer: An In Vitro and In Vivo Study. Cancers. 2021 Jun 25;13(13):3169
NO This work was supported by funds from group CTS-107 (Andalusian Government) and partially by a grant for ISCIII (DTS 17/00081-FEDER). F.Q. acknowledges the FPU2018 grant fromthe Ministerio de Educacion Ciencia y Deporte y Competitividad (Spain).
DS RISalud
RD Apr 6, 2025