期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 36, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.nano.2021.102418
关键词
Radiotherapy; Platelet-activating factor; Lysophosphatidylcholine acyltransferase; Nucleic acid nanoparticles (NANPs); RNA nanotechnology
资金
- National Institute of General Medical Sciences of the National Institutes of Health [R01GM120487, R35GM139587]
- FAPESP-USP SPRINT grant from The Graduate School at the University of North Carolina at Charlotte
- Sao Paulo Research Foundation (FAPESP) [2017/50029-6]
- CNPq [426714/2016-0, 305700/2017-0]
- FAPESP [2013/07937-8]
- CAPES
The study found that simultaneously silencing all four LPCAT transcripts using nucleic acid nanoparticles (NANPs) enhanced the therapeutic effects of radiation in melanoma cells by increasing cell death, reducing long-term cell survival, and activating apoptosis, suggesting that NANPs are an effective strategy for improving radiotherapy efficacy in melanomas.
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. (c) 2021 Elsevier Inc. All rights reserved.
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