Bortezomib Enhances the Antitumor Effects of Interferon-β Gene Transfer on Melanoma Cells
| Autor: | Liliana Maria Elena Finocchiaro, Úrsula A. Rossi, Gerardo C. Glikin |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Canine Bortezomib chemistry.chemical_compound 0302 clinical medicine Cell Movement Tumor Cells Cultured Interferon-Β Cytotoxic T cell Melanoma Lipofection Molecular Structure Cell Cycle Ros Bioquímica y Biología Molecular Cell cycle Medicina Básica 030220 oncology & carcinogenesis Molecular Medicine DNA fragmentation CIENCIAS NATURALES Y EXACTAS Human medicine.drug CIENCIAS MÉDICAS Y DE LA SALUD Cell Survival Antineoplastic Agents Biology Ciencias Biológicas 03 medical and health sciences Structure-Activity Relationship Biología Celular Microbiología medicine Humans Propidium iodide Viability assay Cell Proliferation Pharmacology Dose-Response Relationship Drug Ciencias Veterinarias Genetic Therapy Interferon-beta medicine.disease Molecular biology 030104 developmental biology chemistry CIENCIAS AGRÍCOLAS Apoptosis Liposomes Cancer research Spheroids Drug Screening Assays Antitumor Reactive Oxygen Species |
| Zdroj: | Anti-cancer agents in medicinal chemistry. 17(5) |
| ISSN: | 1875-5992 |
| Popis: | We evaluated the cytotoxic effects of the combination of bortezomib (BTZ) and interferon-β (IFNβ) gene lipofection on cultured melanoma cells. Four canine mucosal (Ak, Br, Bk and Ol) and two human dermal (A375 and SB2) melanoma cell lines were assayed. BTZ sub-pharmacological concentrations (5 nM) enhanced the cytotoxic effects of IFNβ transgene expression on melanoma cells monolayers and spheroids. The combination was also more effective than the single treatments when assayed for clonogenic survival and cell migration. The combined treatment produced a significant raise of apoptosis evidenced by DNA fragmentation as compared to either BTZ or IFNβ gene lipofection single treatments. Furthermore, BTZ significantly increased the intracellular reactive oxygen species (ROS) generation induced by IFNβ gene transfer in melanoma cells, an effect that was reversed by the addition of the ROS inhibitor N-acetyl-L-cystein. The present work encourages further studies about the potential of the combination of interferon gene transfer with proteasome inhibitors as a new combined therapy for malignant melanoma, both in veterinary and/or human clinical settings. Fil: Rossi, Ursula Amaranta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina Fil: Finocchiaro, Liliana Maria Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina Fil: Glikin, Gerardo Claudio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina |
| Databáze: | OpenAIRE |
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