Cationic lipid: DNA complexes allow bleomycin uptake by melanoma cells

Autor: Gerardo Claudio Glikin, Marcela Solange Villaverde, Liliana M.E. Finocchiaro, Úrsula A. Rossi, María L. Gil-Cardeza
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Biotecnología relacionada con la Salud
chemistry.chemical_compound
SPHEROIDS
Cytotoxic T cell
Dog Diseases
purl.org/becyt/ford/3.4 [https]
Melanoma
Sensitization
Antibiotics
Antineoplastic
Temperature
LIPOPLEXES
General Medicine
respiratory system
CHEMOTHERAPY
BLEOMYCIN
Lipids
Endocytosis
medicine.anatomical_structure
purl.org/becyt/ford/3 [https]
lipids (amino acids
peptides
and proteins)
CIENCIAS MÉDICAS Y DE LA SALUD
Cell Survival
Biological Transport
Active
Biology
Bleomycin
Biotecnología de la Salud
Inhibitory Concentration 50
Dogs
Cations
Cell Line
Tumor
medicine
Animals
IC50
Pharmacology
Acid phosphatase
DNA
Genetic Therapy
medicine.disease
Molecular biology
respiratory tract diseases
carbohydrates (lipids)
chemistry
CANINE MELANOMA
Drug Resistance
Neoplasm
Cell culture
Liposomes
biology.protein
Zdroj: CONICET Digital (CONICET)
Consejo Nacional de Investigaciones Científicas y Técnicas
instacron:CONICET
Popis: Bleomycin is a chemotherapeutic agent barely diffusible through the plasmatic membrane. We evaluated DNA/cationic lipids complexes (lipoplexes) as mediators of its uptake in four spontaneous canine melanoma derived cell lines (Ak, Bk, Br and Rkb). Cell survival after lipofection plus or minus bleomycin was determined by the acid phosphatase method and the cellular uptake of lipoplexes, carrying the E. coli β-galactosidase gene, was evidenced by SYBR Green I staining. The four cell lines resulted sensitive to the bleomycin/lipoplexes system in both spatial configurations. Survival rates values were lower than 20% in monolayers of the four tested lines and lower than 30% in three lines (Ak, Bk and Rkb) when grown as spheroids. The sensitization to bleomycin depended on lipoplexes in Ak and Rkb while Bk (in both spatial configurations) and Br (as monolayers) were sensitive to bleomycin alone. Although some degree of sensitivity to bleomycin was induced by cationic lipids alone in Ak and Rkb monolayers, the maximal bleomycin effects appeared in the presence of lipoplexes. The sensitization was independent of transcriptional activity. The co-administration of lipoplexes diminished bleomycin IC50: 10-fold in Ak and Rkb monolayers; and sensitized the Ak and Rkb resistant spheroids. The bleomycin cytotoxic effects depended on lipoplexes concentration and diminished when cells were incubated at 8 °C. Our results suggest that lipoplexes sensitize cells to bleomycin, increasing its uptake by an active transport mechanism, such as endocytosis. The bleomycin/lipoplexes system appears as a promising combination of chemotherapy and non-viral cancer gene therapy. Fil: Gil Cardeza, Maria Lourdes. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Dr. Ángel Roffo". Unidad de Transferencia Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Rossi, Ursula Amaranta. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Dr. Ángel Roffo". Unidad de Transferencia Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Villaverde, Marcela Solange. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Dr. Ángel Roffo". Unidad de Transferencia Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Glikin, Gerardo Claudio. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Dr. Ángel Roffo". Unidad de Transferencia Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Finocchiaro, Liliana Maria Elena. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Dr. Ángel Roffo". Unidad de Transferencia Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Databáze: OpenAIRE
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