3BDO inhibits the proliferation, epithelial-mesenchymal transition (EMT), and stemness via suppressing survivin in human glioblastoma cells.
3BDO inhibits the proliferation, epithelial-mesenchymal transition (EMT), and stemness via suppressing survivin in human glioblastoma cells.
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3BDO 通过抑制人胶质母细胞瘤细胞中的生存素来抑制增殖、上皮间质转化 (EMT) 和干性
DOI：
10.7150/jca.66674
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发表时间：
2022
影响因子：
3.9
通讯作者：
Wang Y
中科院分区：
文献类型：
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作者：
Wang Z;Li Y;Liu M;Chen D;Lu J;Ji Y;Xing Z;Wang Y
背景：胶质母细胞瘤（GBM）是一种预后极差的中枢神经系统肿瘤。干性和EMT在GBM进展中发挥重要作用。3-苄基-5-（（2-硝基苯氧基）甲基）二氢呋喃-2（3 H）-酮（3BDO）是一种自噬抑制剂，具有抗肺癌活性。然而，3BDO对GBM的影响仍然未知。因此，本研究的目的是探索3BDO对GBM的影响，并探讨潜在的分子机制。方法：CCK-8实验和克隆形成实验检测细胞增殖水平。Transwell法检测细胞迁移和侵袭能力。Western blotting和免疫荧光染色分析蛋白表达水平。使用异种移植小鼠模型来评估3BD 0的体内作用。结果：3BDO对U87和U251细胞的增殖有明显的抑制作用，且呈剂量依赖性。此外，3BDO降低了GSC中球体形成的程度和干性标志物（sox 2、巢蛋白和CD 133）的水平。3BDO还抑制GBM细胞的迁移和侵袭能力，并抑制EMT标志物（N-钙粘蛋白、波形蛋白和snail）。此外，我们发现3BDO下调GBM细胞（U87，U251）和GSC中的survivin表达。此外，生存素的过表达降低了3BDO对EMT、GBM细胞侵袭、迁移和增殖的治疗作用，并降低了GSC的干性。最后，我们证明了3BDO可以抑制使用U87细胞构建的肿瘤异种移植小鼠模型中的肿瘤生长。与体外结果相似，3BDO降低了存活素、EMT标记物的表达和体内干性程度。结论：我们的结果表明，3BDO可以抑制GBM在体外和体内通过下调生存介导的干细胞和EMT。
Background: Glioblastoma (GBM) is a tumor of the central nervous system with an extremely poor prognosis. Stemness and EMT play important roles in GBM progression. 3-benzyl-5-((2-nitrophenoxy) methyl) dihydrofuran-2(3H)-one (3BDO), an autophagy inhibitor, has been reported to exert anti-cancer activities on lung carcinoma. However, the effects of 3BDO on GBM remain unknown. Therefore, the purpose of this study was to explore the effects of 3BDO on GBM and to investigate the underlying molecular mechanisms. Method: CCK-8 experiments and clone formation assays were conducted to determine the level of cell proliferation. Transwell assay was conducted to examine cell migration and invasion abilities. Western blotting and immunofluorescence staining were used to analyze protein expression levels. A xenograft mouse model was used to evaluate the effect of 3BDO in vivo. Results: We found that 3BDO inhibited U87 and U251 cell proliferation in a dose-dependent manner. Additionally, 3BDO decreased the degree of sphere formation and levels of stemness markers (sox2, nestin, and CD133) in GSCs. 3BDO also inhibited migration and invasion abilities and suppressed EMT markers (N-cadherin, vimentin, and snail) in GBM cells. Moreover, we found that 3BDO downregulated the expression of survivin in both GBM cells (U87, U251) and GSCs. Furthermore, overexpression of survivin decreased the therapeutic effect of 3BDO on EMT, invasion, migration, and proliferation of GBM cells, as well as decreased the stemness of GSCs. Finally, we demonstrated that 3BDO could inhibit tumor growth in a tumor xenograft mouse model constructed using U87 cells. Similar to the in vitro findings, 3BDO decreased the expression of survivin, EMT makers, and the degree of stemness in vivo. Conclusions: Our results demonstrate that 3BDO can repress GBM both in vitro and in vivo via downregulating survivin-mediated stemness and EMT.
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影响因子：
4.6
作者：
Pu, Wenjun;Qiu, Jiawen;Parat, Marie-Odile
通讯作者：
Parat, Marie-Odile
影响因子：
6.3
作者：
Meng, N.;Peng, N.;Miao, J.
通讯作者：
Miao, J.
影响因子：
5.6
作者：
Le TBU;Vu TC;Ho RZW;Prawira A;Wang L;Goh BC;Huynh H
通讯作者：
Huynh H
DOI：
10.1158/1078-0432.ccr-12-0647
发表时间：
2013-02-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Guvenc H;Pavlyukov MS;Joshi K;Kurt H;Banasavadi-Siddegowda YK;Mao P;Hong C;Yamada R;Kwon CH;Bhasin D;Chettiar S;Kitange G;Park IH;Sarkaria JN;Li C;Shakhparonov MI;Nakano I
通讯作者：
Nakano I
影响因子：
9
作者：
通讯作者：
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