Natural killer cell-derived exosome-entrapped paclitaxel can enhance its anti-tumor effect.

紫杉醇 外体 化学 细胞 微泡 肿瘤细胞 癌症研究 自然杀伤细胞 细胞生物学 生物 医学 细胞毒性 生物化学 化疗 小RNA 内科学 体外 基因
作者
Dali Han,K. Wang,T Zhang,G.-C. Gao,Hui Xu
出处
期刊:DOAJ: Directory of Open Access Journals - DOAJ 卷期号:24 (10): 5703-5713 被引量:42
标识
DOI:10.26355/eurrev_202005_21362
摘要

To study the effectiveness of natural killer cell-derived exosome (NK-Exos)-entrapped paclitaxel (PTX-NK-Exos) in enhancing its anti-tumor effect.The NK-Exos were isolated through ultra-high-speed centrifugation, and the PTX-NK-Exos system was constructed via electroporation. The morphology, particle size, Zeta potential and entrapment rate of PTX-NK-Exos were evaluated using transmission electron microscope (TEM), dynamic light scattering (DLS), Western blotting and high-performance liquid chromatography (HPLC), respectively. The uptake of Exos in human breast cancer MCF-7 cells was observed under a laser confocal microscope. Moreover, the effect of PTX-NK-Exos on MCF-7 cell viability was determined through methyl thiazolyl tetrazolium (MTT) assay, flow cytometry and 4',6-diamidino-2-phenylindole (DAPI) staining. The effects of PTX-NK-Exos on messenger ribonucleic acid (mRNA) and protein expressions of B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax) and Caspase-3 in MCF-7 cells were detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting, respectively.The NK-Exos were successfully isolated via ultra-high-speed centrifugation, and they had uniform particle size and high expression of markers for Exos. MCF-7 cells could take up Exos. The PTX-NK-Exos drug delivery system was successfully prepared using electroporation. In PTX group and NK-Exos group, the proliferation of MCF-7 cells declined, the nuclear apoptosis was evident and the apoptosis rate of MCF-7 cells rose compared with those in Control group. In PTX group and PTX-NK-Exos group, the migration of MCF-7 cells declined compared with that in Control group. According to the results of qRT-PCR and Western blotting, PTX-NK-Exos exerted an anti-tumor effect through inducing the up-regulation of Bax and Caspase-3 in the apoptotic signaling pathway in tumor cells.Exos isolated through ultra-high-speed centrifugation can be used to prepare the PTX-NK-Exos drug delivery system through electroporation. Drug-loaded Exos can effectively inhibit proliferation and induce apoptosis of tumor cells, thereby exerting an anti-tumor effect.
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