基于 DNA 结合穿膜肽的 TRAIL 过表达抑制脂肪组织来源间充质干细胞中胶质瘤 U251MG 的生长。

DNA-binding Cell-penetrating Peptide-based TRAIL Over-expression in Adipose Tissue-derived Mesenchymal Stem Cells Inhibits Glioma U251MG Growth.

机构信息

Department of Neurosurgery, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.

Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.

出版信息

Anticancer Res. 2021 Jun;41(6):2859-2866. doi: 10.21873/anticanres.15067.

DOI:10.21873/anticanres.15067

PMID:34083276

Abstract

BACKGROUND/AIM: Genetic manipulation of stem cells using non-viral vectors is still limited due to low transfection efficiency. We investigated whether the DNA-binding cell-permeation peptides (CPP) can enhance the transfection efficiency of non-viral vectors in adipose tissue-derived mesenchymal stem cells (ASCs) and whether ASCs over-expressing TRAIL through CPP can inhibit the growth of glioma U251MG cells in vitro and in vivo.

MATERIALS AND METHODS

ASCs were genetically engineered to over-express TRAIL by using CPP, pCMV3-TRAIL and lipid-based transfection reagents (X-tremeGENE).

RESULTS

The transfection efficiency of ASCs increased by approximately 7% using CPP; 53.9% of ASCs were transfected and TRAIL expression in ASCs increased by approximately 3 times compared to X-tremeGENE alone. ASCs over-expressing TRAIL using CPP inhibited growth of glioma U251MG cells both in vitro and in the U251MG xenograft model.

CONCLUSION

CPP can be used as an enhancer for genetically manipulating ASCs and tumor treatment.

摘要

背景/目的：由于转染效率低，利用非病毒载体对干细胞进行基因操作仍然受到限制。我们研究了 DNA 结合细胞穿透肽（CPP）是否可以提高脂肪组织来源的间充质干细胞（ASCs）中非病毒载体的转染效率，以及通过 CPP 过表达 TRAIL 的 ASCs 是否可以抑制体外和体内神经胶质瘤 U251MG 细胞的生长。

材料和方法

利用 CPP、pCMV3-TRAIL 和脂质转染试剂（X-tremeGENE）对 ASCs 进行基因工程改造以过表达 TRAIL。

结果

使用 CPP 可使 ASCs 的转染效率提高约 7%；53.9%的 ASCs 被转染，与单独使用 X-tremeGENE 相比，ASCs 中 TRAIL 的表达增加了约 3 倍。CPP 过表达 TRAIL 的 ASCs 可抑制体外和 U251MG 异种移植模型中神经胶质瘤 U251MG 细胞的生长。