Dual targeting of glioblastoma multiforme with a proteasome inhibitor (Velcade) and a phosphatidylinositol 3-kinase inhibitor (ZSTK474).
Dual targeting of glioblastoma multiforme with a proteasome inhibitor (Velcade) and a phosphatidylinositol 3-kinase inhibitor (ZSTK474).
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使用蛋白酶体抑制剂 (Velcade) 和磷脂酰肌醇 3-激酶抑制剂 (ZSTK474) 双重靶向多形性胶质母细胞瘤
DOI：
10.3892/ijo.2013.2205
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发表时间：
2014-02
影响因子：
5.2
通讯作者：
Koeffler HP
中科院分区：
文献类型：
--
作者：
Lin L;Gaut D;Hu K;Yan H;Yin D;Koeffler HP
蛋白酶体抑制剂已被证明是许多肿瘤模型中有效的抗癌化合物，包括多形性胶质母细胞瘤(GBM)。在本研究中，我们发现蛋白酶体抑制剂VELCADE(PS-341/bortezomib)在激活PI3K/Akt通路的同时导致GBM细胞死亡。因此，我们试图研究PI3K抑制剂ZSTK474是否会增强VELCADE在抗癌治疗中的效果。用两种GBM细胞株体外检测VELCADE和ZSTK474单独或联合应用的作用。VELCADE与ZSTK474联合应用可协同抑制GBM细胞的增殖。Annexin V分析显示，VELCADE和ZSTK474联合作用后，细胞凋亡率增加。免疫印迹分析显示，两种药物均可下调p-Akt、p-4EBP1和p-mTOR蛋白的表达。因此，VELCADE与PI3K途径抑制剂ZSTK474联合应用对多形性胶质母细胞瘤的抗癌作用增强。
Proteasome inhibitors have been proven to be effective anticancer compounds in many tumor models, including glioblastoma multiforme (GBM). In this study, we found that the proteasome inhibitor Velcade (PS-341/bortezomib) caused GBM cell death while simultaneously activating the PI3K/Akt pathway. Therefore, we sought to investigate if the PI3K inhibitor ZSTK474 would enhance the effectiveness of Velcade in anticancer therapy. Two GBM cell lines were used to detect the effects of Velcade and ZSTK474 alone or in combination in vitro. The combination of Velcade and ZSTK474 synergistically inhibited the proliferation of GBM cell lines. Cell apoptosis was increased when exposed to Velcade and ZSTK474 in combination as shown by Annexin V analysis. Treatment with both drugs led to downregulation of the p-Akt, p-4EBP1 and p-mTOR proteins as determined by western blot analysis. The anticancer ability of Velcade for glioblastoma multiforme was, therefore, enhanced by combination with the PI3K pathway inhibitor ZSTK474 in glioblastoma multiforme.
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影响因子：
45.3
作者：
Chakravarti, A;Zhai, G;Loeffler, JS
通讯作者：
Loeffler, JS
影响因子：
37.3
作者：
Krakstad C;Chekenya M
通讯作者：
Chekenya M
DOI：
10.1016/s1054-3589(08)57003-7
发表时间：
2009-01-01
期刊：
CONTEMPORARY ASPECTS OF BIOMEDICAL RESEARCH: DRUG DISCOVERY
影响因子：
--
作者：
Ruggeri, Bruce;Miknyoczki, Sheila;Hui, Ai-Min
通讯作者：
Hui, Ai-Min
影响因子：
8
作者：
Yin, D;Zhou, H;Koeffler, HP
通讯作者：
Koeffler, HP
影响因子：
30.8
作者：
Shayesteh, L;Lu, YL;Gray, JW
通讯作者：
Gray, JW