Back to Search
Start Over
PLGA/poloxamer nanoparticles loaded with EPAS1 siRNA for the treatment of pancreatic cancer in vitro and in vivo
- Source :
- International Journal of Molecular Medicine. 35:995-1002
- Publication Year :
- 2015
- Publisher :
- Spandidos Publications, 2015.
-
Abstract
- Endothelial PAS domain protein 1 (EPAS1) is a hypoxia-inducible protein that contributes to tumor progression. Hypoxia is involved in tumor aggressiveness and resistance to chemotherapy and ionizing radiation. In this study, we aimed to assess the effects of EPAS1 silencing using polyethylenimine-poly(lactide-coglycolide) (PLGA)/poloxamer nanoparticles loaded with EPAS1 siRNA on BxPC-3 pancreatic cancer cells and in a mouse model of ectopic pancreatic cancer. PLGA/poloxamer nanoparticles loaded with EPAS1 siRNA or scramble siRNA were prepared using the emulsion/solvent evaporation method. BxPC-3 pancreatic cancer cells were cultured under hypoxic conditions and treated with or without the nanoparticles. MTT and apoptosis assays were then performed. A xenograft nude mouse model of pancreatic cancer was established and the mice were treated with or without the nanoparticles. The mRNA and protein expression levels of EPAS1 in the tumor tissues were determined by semi-quantitative RT-PCR and western blot analysis, respectively. Vascular endothelial growth factor (VEGF) and tumor microvessel density indicated by CD34 were determined by immunohistochemistry. The in vitro release of EPAS1 siRNA from the nanoparticles exerted a sustained-release effect. EPAS1 siRNA nanoparticles inhibited BxPC-3 cell proliferation, and induced cell apoptosis under hypoxic conditions, compared with the nanoparticles loaded with scramble siRNA (all P
- Subjects :
- Male
Apoptosis
Poloxamer
Mice
chemistry.chemical_compound
Nude mouse
Polylactic Acid-Polyglycolic Acid Copolymer
In vivo
Cell Line, Tumor
Pancreatic cancer
Basic Helix-Loop-Helix Transcription Factors
Genetics
medicine
Animals
Humans
Lactic Acid
RNA, Small Interfering
Hypoxia
Cell Proliferation
Neovascularization, Pathologic
Oncogene
biology
General Medicine
biology.organism_classification
medicine.disease
Xenograft Model Antitumor Assays
Molecular biology
Tumor Burden
Gene Expression Regulation, Neoplastic
Pancreatic Neoplasms
Vascular endothelial growth factor
Disease Models, Animal
PLGA
chemistry
Tumor progression
Cancer research
Nanoparticles
RNA Interference
Polyglycolic Acid
Subjects
Details
- ISSN :
- 1791244X and 11073756
- Volume :
- 35
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Medicine
- Accession number :
- edsair.doi.dedup.....cf942dede3cc19ac2e4a521d4811e67b