Simultaneous silencing of lysophosphatidylcholine acyltransferases 1-4 by nucleic acid nanoparticles (NANPs) improves radiation response of melanoma cells
العنوان: | Simultaneous silencing of lysophosphatidylcholine acyltransferases 1-4 by nucleic acid nanoparticles (NANPs) improves radiation response of melanoma cells |
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المؤلفون: | Morgan Chandler, Maria Cristina Rangel, Roger Chammas, Marcos Yukio Yoshinaga, Kirill A. Afonin, Adriano B. Chaves-Filho, Tatiane Katsue Furuya, Alexis Murillo Carrasco, Luciana Nogueira de Sousa Andrade, Silvina Odete-Bustos, Justin R. Halman, Renata F. Saito, Sayuri Miyamoto |
المصدر: | Nanomedicine Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
بيانات النشر: | Elsevier BV, 2021. |
سنة النشر: | 2021 |
مصطلحات موضوعية: | Programmed cell death, Cell, Biomedical Engineering, Pharmaceutical Science, Medicine (miscellaneous), Bioengineering, 02 engineering and technology, APOPTOSE, Article, 03 medical and health sciences, chemistry.chemical_compound, Cell Line, Tumor, Nucleic Acids, Radioresistance, medicine, Humans, Gene silencing, General Materials Science, Gene Silencing, Melanoma, 030304 developmental biology, 0303 health sciences, Platelet-activating factor, Chemistry, 1-Acylglycerophosphocholine O-Acyltransferase, 021001 nanoscience & nanotechnology, medicine.disease, Neoplasm Proteins, Lysophosphatidylcholine, medicine.anatomical_structure, Apoptosis, Cancer research, RNA, Nanoparticles, Molecular Medicine, lipids (amino acids, peptides, and proteins), 0210 nano-technology |
الوصف: | Radiation induces the generation of platelet-activating factor receptor (PAF-R) ligands, including PAF and oxidized phospholipids. Alternatively, PAF is also synthesized by the biosynthetic enzymes lysophosphatidylcholine acyltransferases (LPCATs) which are expressed by tumor cells including melanoma. The activation of PAF-R by PAF and oxidized lipids triggers a survival response protecting tumor cells from radiation-induced cell death, suggesting the involvement of the PAF/PAF-R axis in radioresistance. Here, we investigated the role of LPCATs in the melanoma cell radiotherapy response. LPCAT is a family of four enzymes, LPCAT1-4, and modular nucleic acid nanoparticles (NANPs) allowed for the simultaneous silencing of all four LPCATs. We found that the in vitro simultaneous silencing of all four LPCAT transcripts by NANPs enhanced the therapeutic effects of radiation in melanoma cells by increasing cell death, reducing long-term cell survival, and activating apoptosis. Thus, we propose that NANPs are an effective strategy for improving radiotherapy efficacy in melanomas. |
تدمد: | 1549-9634 |
DOI: | 10.1016/j.nano.2021.102418 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dee39f07a5be9554f35fa81baec8010b https://doi.org/10.1016/j.nano.2021.102418 |
Rights: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....dee39f07a5be9554f35fa81baec8010b |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15499634 |
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DOI: | 10.1016/j.nano.2021.102418 |