AS1411-Induced Growth Inhibition of Glioma Cells by Up-Regulation of p53 and Down-Regulation of Bcl-2 and Akt1 via Nucleolin.
AS1411-Induced Growth Inhibition of Glioma Cells by Up-Regulation of p53 and Down-Regulation of Bcl-2 and Akt1 via Nucleolin.
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AS1411 通过核仁蛋白上调 p53 并下调 Bcl-2 和 Akt1 诱导神经胶质瘤细胞的生长抑制
DOI：
10.1371/journal.pone.0167094
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Cheng Y;Zhao G;Zhang S;Nigim F;Zhou G;Yu Z;Song Y;Chen Y;Li Y
AS 1411结合核仁素（NCL），是第一个达到I期和II期临床试验的寡脱氧核苷酸适体，用于治疗多种癌症。然而，AS 1411靶向和杀死胶质瘤细胞和组织的机制仍不清楚。在这里，我们报告，AS 1411诱导细胞凋亡和周期阻滞，并通过上调p53和下调Bcl-2和Akt 1抑制细胞活力在人脑胶质瘤细胞。与正常人星形胶质细胞（NHA）相比，NCL在人脑胶质瘤U87、U251和SHG 44细胞的细胞核和细胞质中均过表达。AS 1411与NCL结合，抑制胶质瘤细胞增殖，但对NHA无抑制作用，并伴有p53上调，Bcl-2和Akt 1下调。此外，AS 1411处理导致胶质瘤细胞中G2/M细胞周期停滞，然而，过表达NCL可消除该现象。此外，AS 1411诱导细胞凋亡，这是通过沉默p53和过度表达Bcl-2来阻止的。此外，AS 1411以Akt 1依赖的方式抑制胶质瘤细胞的迁移和侵袭。重要的是，AS 1411抑制胶质瘤异种移植物的生长，并延长胶质瘤荷瘤小鼠的存活时间。这些结果表明，寡脱氧核苷酸适体治疗胶质瘤的前景。
AS1411 binds nucleolin (NCL) and is the first oligodeoxynucleotide aptamer to reach phase I and II clinical trials for the treatment of several cancers. However, the mechanisms by which AS1411 targets and kills glioma cells and tissues remain unclear. Here we report that AS1411 induces cell apoptosis and cycle arrest, and inhibits cell viability by up-regulation of p53 and down-regulation of Bcl-2 and Akt1 in human glioma cells. NCL was overexpressed in both nucleus and cytoplasm in human glioma U87, U251 and SHG44 cells compared to normal human astrocytes (NHA). AS1411 bound NCL and inhibited the proliferation of glioma cells but not NHA, which was accompanied with up-regulation of p53 and down-regulation of Bcl-2 and Akt1. Moreover, AS1411 treatment resulted in the G2/M cell cycle arrest in glioma cells, which was however abolished by overexpression of NCL. Further, AS1411 induced cell apoptosis, which was prevented by silencing of p53 and overexpression of Bcl-2. In addition, AS1411 inhibited the migration and invasion of glioma cells in an Akt1-dependent manner. Importantly, AS1411 inhibited the growth of glioma xenograft and prolonged the survival time of glioma tumor-bearing mice. These results revealed a promising treatment of glioma by oligodeoxynucleotide aptamer.
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影响因子：
4.8
作者：
Griffin, Sian V.;Olivier, J. Paul;Shankland, Stuart J.
通讯作者：
Shankland, Stuart J.
影响因子：
4.8
作者：
Huwiler, A;Akool, ES;Eberhardt, W
通讯作者：
Eberhardt, W
DOI：
10.1111/j.1432-1033.1992.tb17318.x
发表时间：
1992-10-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
GHISOLFI, L;KHARRAT, A;ERARD, M
通讯作者：
ERARD, M
影响因子：
16.6
作者：
Chen, Yong;Qu, Konggang;Qu, Xiaogang
通讯作者：
Qu, Xiaogang
影响因子：
4
作者：
Galzio, R.;Rosati, F.;Cimini, A.
通讯作者：
Cimini, A.