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Int J Mol Sci. 2019 Jan 7;20(1). pii: E191. doi: 10.3390/ijms20010191.

Differential Exosomic Proteomic Patterns and Their Influence in Resveratrol Sensitivities of Glioblastoma Cells.

Author information

1
School of Medicine, South China University of Technology (SCUT), Guangzhou 510000, China. mcnie@mail.scut.edu.cn.
2
Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China. lihongmcn@dlmedu.edu.cn.
3
Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China. moliwusx@sina.com.
4
School of Medicine, South China University of Technology (SCUT), Guangzhou 510000, China. mcsmall@mail.scut.edu.cn.
5
School of Medicine, South China University of Technology (SCUT), Guangzhou 510000, China. 201710106932@mail.scut.edu.cn.
6
School of Medicine, South China University of Technology (SCUT), Guangzhou 510000, China. mcliujia@scut.edu.cn.
7
Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China. mcliujia@scut.edu.cn.

Abstract

Glioblastoma multiforme (GBM) is the commonest primary brain malignancy with extremely poor prognosis. Resveratrol posseses anti-cancer effects, while GBM cells respond differently to it due to certain unknown reason(s). Because the tumor-derived exosomes are supposed to influence chemosensitivity, the exosomic proteins released from resveratrol-sensitive U251 and resveratrol-resistant glioblastoma LN428 cells are profiled before (N/Exo) and after drug treatment (Res/Exo) by label-free liquid chromatography-mass spectrometry (LC-MS). The therapeutic implications of the proteomic findings are estimated by gene ontology enrichment analysis (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG)-based bioinformatic analyses and further elucidated by exosome co-incubating. The results reveal that U251/N/Exo but not U251/Res/Exo enhances resveratrol sensitivity of resveratrol-resistant LN428 cells. The resveratrol sensitive properties of U251 cells are not altered by either LN428/N/Exo or LN428/Res/Exo. U251/N/Exo contains higher levels of chromatin silencing and epidermis development proteins, while U251/Res/Exo has more oxygen transport and G protein-coupled receptor. Both of LN428/N/Exo and LN428/Res/Exo are rich in the proteins related with nucleosome assembly, microtubule-based process and chromatin silencing. In conclusion, U251/N/Exo sensitizes LN428 cells to resveratrol via delivering drug sensitizing signals, suggesting the presence of additional factor(s) that may determine the resveratrol sensitivities of glioblastoma cells.

KEYWORDS:

drug sensitivity; exosome; glioblastoma cells; proteomics; resveratrol

PMID:
30621053
PMCID:
PMC6337327
DOI:
10.3390/ijms20010191
[Indexed for MEDLINE]
Free PMC Article

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