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Apcin 抑制胶质母细胞瘤细胞的生长和侵袭,并提高胶质细胞瘤对替莫唑胺的敏感性。

Apcin inhibits the growth and invasion of glioblastoma cells and improves glioma sensitivity to temozolomide.

机构信息

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

出版信息

Bioengineered. 2021 Dec;12(2):10791-10798. doi: 10.1080/21655979.2021.2003927.

DOI:10.1080/21655979.2021.2003927
PMID:34753395
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8810058/
Abstract

Glioblastoma (GBM) is the most common malignant primary brain tumor, and GBM patients have a poor overall prognosis. CDC20 expression is increased in a variety of tumors and associated with temozolomide (TMZ) resistance in glioma cells. Apcin specifically binds to CDC20 to inhibit APC/C-CDC20 interaction and exhibits antitumor properties. The purpose of this article was to assess whether apcin inhibits tumor growth in glioma cell lines and increases the sensitivity of GBM to TMZ. In this study, a series of biochemical assays, such as Cell Counting Kit-8 (CCK-8), wound healing, apoptosis and colony formation assays, were performed to determine the antitumor properties of apcin in glioma cells. GBM cell apoptosis was detected by western blotting analysis of related proteins. Apcin increased the sensitivity of glioma to TMZ, as confirmed by CCK-8 and western blotting analysis. The results showed that apcin significantly inhibited the proliferation of glioma cells in a time- and dose-dependent manner. The migration decreased with increasing apcin concentrations. Increased Bim expression indicated that apcin promotes the apoptosis of glioma cells. Furthermore, apcin improved glioma sensitivity to TMZ. The results showed that apcin can effectively inhibit GBM growth and improve TMZ sensitivity. Apcin has the potential to treat GBM and is expected to provide new ideas for individualized treatment.

摘要

胶质母细胞瘤(GBM)是最常见的恶性原发性脑肿瘤,GBM 患者总体预后较差。CDC20 的表达在多种肿瘤中增加,并与胶质瘤细胞对替莫唑胺(TMZ)的耐药性相关。Apcin 特异性结合 CDC20 以抑制 APC/C-CDC20 相互作用,并表现出抗肿瘤特性。本文旨在评估 apcin 是否抑制神经胶质瘤细胞系中的肿瘤生长并增加 GBM 对 TMZ 的敏感性。在这项研究中,进行了一系列生化测定,如细胞计数试剂盒-8(CCK-8)、划痕愈合、凋亡和集落形成测定,以确定 apcin 在神经胶质瘤细胞中的抗肿瘤特性。通过相关蛋白的 Western blot 分析检测 GBM 细胞凋亡。CCK-8 和 Western blot 分析证实 apcin 增加了神经胶质瘤对 TMZ 的敏感性。结果表明,apcin 以时间和剂量依赖性方式显著抑制神经胶质瘤细胞的增殖。迁移随着 apcin 浓度的增加而减少。Bim 表达增加表明 apcin 促进神经胶质瘤细胞凋亡。此外,apcin 提高了神经胶质瘤对 TMZ 的敏感性。结果表明,apcin 可有效抑制 GBM 生长并提高 TMZ 敏感性。Apcin 具有治疗 GBM 的潜力,并有望为个体化治疗提供新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8ac/8810058/613cfa87bee5/KBIE_A_2003927_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8ac/8810058/426c17be405e/KBIE_A_2003927_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8ac/8810058/c337d5989ffa/KBIE_A_2003927_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8ac/8810058/613cfa87bee5/KBIE_A_2003927_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8ac/8810058/426c17be405e/KBIE_A_2003927_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8ac/8810058/c337d5989ffa/KBIE_A_2003927_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8ac/8810058/613cfa87bee5/KBIE_A_2003927_F0003_OC.jpg