The Antitumor Activity of Sodium Selenite Alone and in Combination with Gemcitabine in Pancreatic Cancer: An In Vitro and In Vivo Study
| Autor: | Laura Cabeza, Raúl Ortiz, Gloria Perazzoli, Jose Prados, Kevin Doello, Consolación Melguizo, Francisco Quiñonero, Cristina Mesas |
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| Přispěvatelé: | [Doello,K] Medical Oncology Service, Virgen de las Nieves Hospital, Granada, Spain. [Doello,K, Mesas,C, Quiñonero,F, Perazzoli,G, Cabeza,L, Prados,J, Melguizo,C, Ortiz,R] Instituto Biosanitario de Granada (ibs. GRANADA), Granada, Spain. [Mesas,C, Ortiz,R] Center of Biomedical Research (CIBM), Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Granada, Spain. [Quiñonero,F, Ortiz,R] Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada, Spain. [Perazzoli,G] Department of Medicine, Faculty of Health Sciences, University of Almería, Granada, Spain. |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
cancer stem cells
Anatomy::Cells::Cells Cultured::Cell Line::Cell Line Tumor [Medical Subject Headings] 0301 basic medicine Cancer Research Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice Inbred Strains::Mice Inbred C57BL [Medical Subject Headings] pancreatic cancer Anatomy::Cells::Stem Cells::Neoplastic Stem Cells [Medical Subject Headings] Pharmacology medicine.disease_cause Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] 0302 clinical medicine Organisms::Eukaryota::Animals [Medical Subject Headings] Sodium selenite Phenomena and Processes::Metabolic Phenomena::Metabolism::Oxidative Stress [Medical Subject Headings] RC254-282 Chemistry Cancer stem cells gemcitabine Neoplasms. Tumors. Oncology. Including cancer and carcinogens Tratamiento combinado Oncology 030220 oncology & carcinogenesis Selenito de sodio medicine.drug Anticuerpos chemistry.chemical_element Article sodium selenite 03 medical and health sciences combined therapy Cancer stem cell In vivo Pancreatic cancer Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Survival [Medical Subject Headings] medicine Células madre neoplásicas Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings] Neoplasias pancreáticas Phospho-p38 protein Antineoplásicos medicine.disease Gemcitabine In vitro Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::NADH NADPH Oxidoreductases::Apoptosis Inducing Factor [Medical Subject Headings] Diseases::Digestive System Diseases::Pancreatic Diseases::Pancreatic Neoplasms [Medical Subject Headings] 030104 developmental biology Cell culture phospho-p38 protein Selenium Oxidative stress Combined therapy Chemicals and Drugs::Inorganic Chemicals::Sodium Compounds::Sodium Selenite [Medical Subject Headings] |
| Zdroj: | Cancers Volume 13 Issue 13 Digibug. Repositorio Institucional de la Universidad de Granada instname Cancers, Vol 13, Iss 3169, p 3169 (2021) Digibug: Repositorio Institucional de la Universidad de Granada Universidad de Granada (UGR) |
| Popis: | 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. CTS-107 (Andalusian Government) ISCIII (DTS 17/00081-FEDER) FPU - Ministerio de Educacion Ciencia y Deporte y Competitividad (Spain) Scientific Instrumentation Center (CIC) from the Granada University |
| Databáze: | OpenAIRE |
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