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Foxp3 过表达 Treg 细胞对非小细胞肺癌细胞的影响。

The effect of foxp3-overexpressing Treg cells on non-small cell lung cancer cells.

机构信息

Department of Thoracic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510500, P.R. China.

Department of Thoracic Surgery, Shanwei People's Hospital, Shanwei, Guangdong 516600, P.R. China.

出版信息

Mol Med Rep. 2018 Apr;17(4):5860-5868. doi: 10.3892/mmr.2018.8606. Epub 2018 Feb 13.

Abstract

The aim of the present study was to investigate the novel mechanisms of forkhead box protein P3 (foxp3) in T regulatory (Treg) cells in lung cancer behavior. Treg cells were isolated from the peripheral blood of healthy volunteers and then co‑cultured with 95D cells. A plasmid overexpressing foxp3 was constructed and transfected into Treg cells and an MTS assay was performed to assess cell viability. Flow cytometry was performed to evaluate cell apoptosis and reverse transcription‑quantitative polymerase chain reaction was used to measure mRNA expression. A Transwell assay was used to assess cell invasion. Treg cells were successfully isolated from peripheral blood with purity of 94.26%. Foxp3 expression in Treg cells was significantly increased following co‑culture with 95D cells, while matrix metalloproteinase‑9 expression was upregulated in 95D cells co‑cultured with Treg cells. The apoptosis, invasion and migration abilities of 95D cells were suppressed by co‑culture with Treg cells, whereas the adhesive ability was enhanced. Foxp3 overexpression in Treg cells enhanced the viability and invasiveness of 95D cells, whereas cell adhesion and migration were decreased. The results of the present study demonstrate that the viability and invasiveness of 95D cells are enhanced by foxp3 overexpression in Treg cells, indicating that increased levels of foxp3 in the tumor microenvironment may promote tumor cell growth.

摘要

本研究旨在探讨叉头框蛋白 P3(foxp3)在肺癌行为中调节性 T 细胞(Treg)中的新机制。从健康志愿者外周血中分离 Treg 细胞,然后与 95D 细胞共培养。构建过表达 foxp3 的质粒并转染至 Treg 细胞中,通过 MTS assay 评估细胞活力。通过流式细胞术评估细胞凋亡,通过逆转录-定量聚合酶链反应检测 mRNA 表达。通过 Transwell assay 评估细胞侵袭。成功地从外周血中分离出纯度为 94.26%的 Treg 细胞。与 95D 细胞共培养后,Treg 细胞中 foxp3 的表达显著增加,而与 Treg 细胞共培养的 95D 细胞中基质金属蛋白酶-9 的表达上调。与 Treg 细胞共培养可抑制 95D 细胞的凋亡、侵袭和迁移能力,而增强其黏附能力。Treg 细胞中 foxp3 的过表达增强了 95D 细胞的活力和侵袭性,而细胞黏附和迁移能力下降。本研究结果表明,Treg 细胞中 foxp3 的过表达增强了 95D 细胞的活力和侵袭性,提示肿瘤微环境中 foxp3 水平的升高可能促进肿瘤细胞生长。

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