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STAT3 靶向小干扰 RNA 与 AZD0530 联合应用对胶质瘤的体内外抑制作用。

Synergistic effect of STAT3‑targeted small interfering RNA and AZD0530 against glioblastoma in vitro and in vivo.

机构信息

Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin 300050, P.R. China.

English Department, International Medical School, Tianjin Medical University, Tianjin 300070, P.R. China.

出版信息

Mol Med Rep. 2019 Oct;20(4):3625-3632. doi: 10.3892/mmr.2019.10596. Epub 2019 Aug 21.

DOI:10.3892/mmr.2019.10596
PMID:31485668
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6755172/
Abstract

The aim of this study was to explore the synergistic effect of signal transducer and activator of transcription 3 (STAT3)‑targeted small interfering (si)RNA and AZD0530 against glioblastoma in vitro and in vivo. Glioblastoma cell lines U87 and U251 were divided into four groups and treated with control, LV‑STAT3 siRNA, AZD0530, and combined LV‑STAT3 siRNA with AZD0530, respectively. The proliferation and apoptotic capacity of glioblastoma cells was assessed by Cell Counting Kit‑8 and double staining flow cytometry assays, respectively. Additionally, the potential effect of LV‑STAT3 siRNA and AZD0530 on glioblastoma was evaluated in vivo. Images were captured of the tumor formation in mice every week. Following three weeks of treatment, NMR scan and immunohistochemistry were performed. The treatment of combined LV‑STAT3 siRNA and AZD0530 was more effective in inhibiting proliferation and inducing apoptosisof glioblastoma cells in comparison with the treatment of either LV‑STAT3 siRNA or AZD0530 alone. Although LV‑STAT3 siRNA or AZD0530 treatment alone suppressed tumor growth in mice, the combined treatment had a more significant effect than the treatment of LV‑STAT3 siRNA or AZD0530 alone. According to the results of both in vitro and in vivo assays, a combined therapy of LV‑STAT3 siRNA with AZD0530 could enhance therapeutic effects on glioblastoma, supporting the idea that the combination of LV‑STAT3 siRNA and AZD0530 could serve as a novel and effective strategy to combat glioblastoma.

摘要

本研究旨在探讨信号转导和转录激活因子 3(STAT3)靶向小干扰(si)RNA 与 AZD0530 联合应用对体外和体内胶质母细胞瘤的协同作用。将胶质母细胞瘤细胞系 U87 和 U251 分为四组,分别用对照、LV-STAT3 siRNA、AZD0530 和 LV-STAT3 siRNA 联合 AZD0530 处理。通过细胞计数试剂盒-8 和双染色流式细胞术检测分别评估胶质母细胞瘤细胞的增殖和凋亡能力。此外,还在体内评估了 LV-STAT3 siRNA 和 AZD0530 对胶质母细胞瘤的潜在影响。每周对小鼠肿瘤形成情况进行图像采集。治疗 3 周后,进行 NMR 扫描和免疫组织化学检查。与单独使用 LV-STAT3 siRNA 或 AZD0530 相比,联合使用 LV-STAT3 siRNA 和 AZD0530 更能有效抑制胶质母细胞瘤细胞的增殖并诱导其凋亡。虽然单独使用 LV-STAT3 siRNA 或 AZD0530 治疗能抑制小鼠肿瘤生长,但联合治疗的效果比单独使用 LV-STAT3 siRNA 或 AZD0530 更显著。根据体外和体内实验的结果,LV-STAT3 siRNA 与 AZD0530 的联合治疗可能增强对胶质母细胞瘤的治疗效果,支持 LV-STAT3 siRNA 与 AZD0530 联合应用可能作为治疗胶质母细胞瘤的一种新的有效策略的观点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46d2/6755172/903bb79a7939/MMR-20-04-3625-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46d2/6755172/b96d4319b6cc/MMR-20-04-3625-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46d2/6755172/9e60b4154ec2/MMR-20-04-3625-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46d2/6755172/57398ee25fb4/MMR-20-04-3625-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46d2/6755172/903bb79a7939/MMR-20-04-3625-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46d2/6755172/b96d4319b6cc/MMR-20-04-3625-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46d2/6755172/9e60b4154ec2/MMR-20-04-3625-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46d2/6755172/57398ee25fb4/MMR-20-04-3625-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46d2/6755172/903bb79a7939/MMR-20-04-3625-g03.jpg

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