si-PDGFR β-Loaded Exosomes Suppress the Progression of Glioma by Inhibiting the Oxidative Associated PI3K/Akt/EZH2 Signaling Pathway

si-PDGFR β 负载外泌体通过抑制氧化相关的 PI3K/Akt/EZH2 信号通路抑制胶质瘤进展

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作者:Yuping Li, Hailong Yu, Qiang Ma, Min Wei, Xiaoguang Liu, Yajie Qi, Chen Li, Lun Dong, Hengzhu Zhang

Abstract

This study investigated the possibility of exosomes loaded with si-PDGFRβ ability to suppress the progression of glioma. Common gliomas develop from neuroglial progenitor cells. Many variables affect the survival rate and occurrence of gliomas. Understanding oxidative stress processes and creating new, efficient treatments are crucial because oxidative stress is linked to the development of brain tumors. For this purpose, selected clinical samples were subjected to various tests like quantitative real-time PCR, Cignal Finder RTK signaling 7-pathway reporter array analysis, CCK-8 analysis, flow cytometry, and immunoblotting. Here, we demonstrated that PDGFRβ expression was increased in glioma patients. Following that, cell-derived exosomes were extracted and collected and traced in vivo, and selected tissue samples were subjected to immunohistochemical analysis. The results indicated that the knockdown of PDGFRβ (si-PDGFRβ) inhibited the proliferation of glioma cells. Besides this, si-PDGFRβ-loaded exosomes induced a similar antitumor effect in glioma cells. The anticancer effect of si-PDGFRβ-loaded exosomes was mediated by the inactivation of the PI3K/Akt/EZH2 pathway. Finally, we verified that this exosome delivery system, si-PDGFRβ-loaded exosomes, had robust targeting and no associated toxicity. In conclusion, the study confirmed that si-PDGFRβ-loaded exosomes inhibit glioma progression via inactivating the PI3K/Akt/EZH2 signaling pathway.

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