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Published on: April 16, 2019
Grape-derived exosome-like nanoparticles suppress nasopharyngeal carcinoma progression by targeting the FASN/MAPK
Yi Zhang1, Liying Zheng2, Gaohan Zhu1
1School of Gongli Hospital Medical Technology, University of Shanghai for Science and Technology, Shanghai 200093, China; Department of Otorhinolaryngology Head and Neck Surgery, Pudong Gongli Hospital, Shanghai University of Medicine & Health Sciences, Shanghai 200135, China.
Abstract:
Nasopharyngeal carcinoma (NPC) is an epithelial malignancy with distinct geographic clustering, highly prevalent in southern China and Southeast Asia. Grape-derived exosome-like nanoparticles (GELNs) represent a promising natural delivery platform for cancer intervention; however, the intrinsic resveratrol (RSV) of GELNs and their regulatory effects on lipid metabolism in NPC remain poorly defined. In this study, GELNs were isolated from grape peels by ultracentrifugation and characterized morphologically and biochemically. The therapeutic efficacy of GELNs-RSV was evaluated in HNE-1 cells and nude mouse xenografts using CCK-8, Transwell, in vivo imaging and histological analyses. Transcriptomic profiling, pathway enrichment and gain-of-function experiments were applied to dissect molecular mechanisms. Results revealed that GELNs effectively delivered RSV into NPC cells, and markedly attenuated cell proliferation, migration and xenograft tumor growth. Mechanistically, GELNs-RSV repressed fatty acid synthase (FASN) expression and inactivated the MAPK pathway via decreased ERK phosphorylation, thereby disrupting lipid metabolism and constraining NPC progression. These findings identify GELNs as a natural RSV delivery system that targets the FASN/MAPK axis, providing preclinical evidence for the development of novel NPC therapeutic strategies.
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