Antineoplastic effect of 1α,25(OH)2D3 in spheroids from endothelial cells transformed by Kaposi’s sarcoma-associated herpesvirus G protein coupled receptor
| Autor: | Cinthya Tapia, Alejandra Suares, Verónica González-Pardo |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Endocrinology Diabetes and Metabolism Clinical Biochemistry Biology medicine.disease_cause Biochemistry Ciencias Biológicas 03 medical and health sciences 0302 clinical medicine Endocrinology ANTINEOPLASTIC EFFECTS medicine MULTICELULAR SPHEROIDS Active Vitamin D Kaposi's sarcoma-associated herpesvirus ACTIVE VITAMIN D Molecular Biology G protein-coupled receptor Spheroid Cell Biology vGPCR Bioquímica y Biología Molecular Molecular biology 030104 developmental biology 030220 oncology & carcinogenesis Molecular Medicine Multicellular spheroid CIENCIAS NATURALES Y EXACTAS |
| Zdroj: | The Journal of Steroid Biochemistry and Molecular Biology. 186:122-129 |
| ISSN: | 0960-0760 |
| DOI: | 10.1016/j.jsbmb.2018.10.004 |
| Popis: | The Kaposi´s sarcoma-associated herpesvirus G protein-coupled receptor (KSHV/vGPCR) is a key molecule in the pathogenesis of Kaposi´s sarcoma. In endothelial cells, tumor maintenance and NF-κB activation depends on vGPCR constitutive expression and activity. We have previously demonstrated that 1α,25(OH)2D3 induces apoptosis in a VDR dependent manner, inhibits vGPCR cell growth and NF-κB activity. In this study, we developed a method to obtain multicellular spheroids (MCS) from endothelial cells expressing vGPCR in order to test whether MCS have a similar response to 2D-cultures after 1α,25(OH)2D3 treatment. Firstly, we found that vGPCR MCS started to form at 2nd day-growth, reaching a diameter up to 300 μm at 7th day-growth, whereas cells without vGPCR expression (SVEC) developed spheroids earlier and remained smaller throughout the period monitored. Secondly, vGPCR MCS size and architecture were analyzed during 1α,25(OH)2D3 (0.1-100 nM, 48 h) treatment. We found that once treated with 10 nM of 1α,25(OH)2D3 the initials MCS began a slight disaggregation with no changes in size; whereas at the higher dose (100 nM) the architecture of MCS was found completely broken. Furthermore, VDR mRNA expression increased significantly and this change was accompanied by a reduction of HIF-1α, an increase of VEGF, p21 and Bim mRNA expression. Finally, results from Western blot analysis showed that 1α,25(OH)2D3 decreased Akt and ERK1/2 protein phosphorylation. In conclusion, these data have revealed that 1α,25(OH)2D3 inhibits vGPCR MCS proliferation and induces apoptosis similar to vGPCR cells growing in 2D-cultures. Fil: Suares, Alejandra Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina Fil: Tapia, Cinthya Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina Fil: González Pardo, María Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina |
| Databáze: | OpenAIRE |
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