Abstract 10P
Background
Sodium selenite is a selective cytotoxic agent for tumor cells. This cytotoxicity is due to the depletion of reduced glutathione and thioredoxin, leaving the cell defenseless against oxidative stress. Pancreatic cancer is the ninth most frequent and the fourth deadliest. It has a low response to treatment (chemotherapy), which makes it necessary to develop new therapeutic strategies. The objective of this study is to demonstrate in vitro and in vivo antitumor ability of sodium selenite against pancreatic cancer.
Methods
Pancreatic adenocarcinoma cell lines PANC-1 (human) and Pan02 (murine) were exposed to selenite and selenite + gemcitabine (GMZ) both in monolayer culture and after the generation of multicellular spheroids (MTS). In vivo studies were performed by generating tumors in C57BL mice after subcutaneous inoculation of the Pan02 line. In addition, immunofluorescence, Western-Blot and mitochondrial membrane potential studies were performed to elucidate the molecular mechanisms by which sodium selenite acts. Finally, the effect of treatment on cancer stem cells (CSCs) derived from tumor lines was assessed.
Results
The results showed an IC50 of 5.6 μM and 4.6 μM in PANC-1 and Pan02 lines, respectively, and a synergistic effect when associated with GMZ. The antitumor effect of sodium selenite involved apoptosis-inducing factor (AIF) in monotherapy and phospho-p38 expression in combination with GMZ. In addition, sodium selenite alone and in association with GMZ significantly decreased migration and colony forming ability, reduced tumor viability in multicellular tumor spheroids (MTS) and decreased CSCs sphere formation. In vivo studies showed that the combined therapy inhibits tumor growth (65%) compared to the untreated group and also compared to sodium selenite or GMZ used as monotherapy (up to 40%), increasing mice survival. These results were supported by analysis of C57BL/6 albino mice bearing a Pan02-generated tumor using the IVIS system.
Conclusions
In conclusion, sodium selenite is a potential agent for the treatment of pancreatic cancer and could be considered for future clinical trials in humans.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
UGR.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.