Cell division cycle 7-kinase inhibitor PHA-767491 hydrochloride suppresses glioblastoma growth and invasiveness.
Cell division cycle 7-kinase inhibitor PHA-767491 hydrochloride suppresses glioblastoma growth and invasiveness.
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DOI：
10.1186/s12935-016-0364-8
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发表时间：
2016
影响因子：
5.8
通讯作者：
Erkan EP
中科院分区：
文献类型：
--
作者：
Erbayraktar Z;Alural B;Erbayraktar RS;Erkan EP
基因组不稳定是癌细胞的一个特征，这种细胞现象可能是复制应激的结果。利用复制压力，并以一种有针对性的方式增强它来对抗癌细胞是可能的。其中一种策略涉及靶向细胞分裂周期7相关蛋白激酶（CDC7），这是一种在DNA复制起始调控中起关键作用的蛋白质。CDC7过表达存在于不同的癌症中，CDC7的小分子抑制剂具有良好的抗肿瘤作用。在这里，我们旨在测试CDC7抑制作为胶质母细胞瘤治疗新策略的潜力。以盐酸PHA-767491作为CDC7抑制剂。用2个胶质母细胞瘤细胞系（U87-MG和U251-MG）和一个对照细胞系（3T3）来表征CDC7抑制的效果。分析CDC7抑制对细胞活力、增殖、凋亡、迁移和侵袭的影响。此外，real-time PCR阵列被用于鉴定响应CDC7抑制的差异表达基因。我们的研究结果表明，抑制CDC7可降低胶质母细胞瘤细胞活力，抑制细胞增殖，并引发胶质母细胞瘤细胞系的凋亡。此外，我们确定CDC7抑制也抑制胶质母细胞瘤细胞的迁移和侵袭。为了确定CDC7抑制的分子靶点，我们使用了实时PCR阵列，结果显示了几种mrna和mirna的失调。综上所述，我们的研究结果表明，抑制CDC7是治疗胶质母细胞瘤的一种有希望的策略。本文的在线版本（doi:10.1186/s12935-016-0364-8）包含补充材料，可供授权用户使用。
Genomic instability is a hallmark of cancer cells, and this cellular phenomenon can emerge as a result of replicative stress. It is possible to take advantage of replicative stress, and enhance it in a targeted way to fight cancer cells. One of such strategies involves targeting the cell division cycle 7-related protein kinase (CDC7), a protein with key roles in regulation of initiation of DNA replication. CDC7 overexpression is present in different cancers, and small molecule inhibitors of the CDC7 have well-documented anti-tumor effects. Here, we aimed to test the potential of CDC7 inhibition as a new strategy for glioblastoma treatment. PHA-767491 hydrochloride was used as the CDC7 inhibitor. Two glioblastoma cell lines (U87-MG and U251-MG) and a control cell line (3T3) were used to characterize the effects of CDC7 inhibition. The effect of CDC7 inhibition on cell viability, cell proliferation, apoptosis, migration, and invasion were analyzed. In addition, real-time PCR arrays were used to identify the differentially expressed genes in response to CDC7 inhibition. Our results showed that CDC7 inhibition reduces glioblastoma cell viability, suppresses cell proliferation, and triggers apoptosis in glioblastoma cell lines. In addition, we determined that CDC7 inhibition also suppresses glioblastoma cell migration and invasion. To identify molecular targets of CDC7 inhibition, we used real-time PCR arrays, which showed dysregulation of several mRNAs and miRNAs. Taken together, our findings suggest that CDC7 inhibition is a promising strategy for treatment of glioblastoma. The online version of this article (doi:10.1186/s12935-016-0364-8) contains supplementary material, which is available to authorized users.
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影响因子：
16
作者：
Chuang, Li-Chiou;Teixeira, Leonardo K.;Wohlschlegel, James A.;Henze, Martha;Yates, John R.;Mendez, Juan;Reed, Steven I.
通讯作者：
Reed, Steven I.
影响因子：
4.7
作者：
Nambiar, Sandeep;Mirmohammadsadegh, Alireza;Hengge, Ulrich R.
通讯作者：
Hengge, Ulrich R.
影响因子：
--
作者：
Qiu ZK;Shen D;Chen YS;Yang QY;Guo CC;Feng BH;Chen ZP
通讯作者：
Chen ZP
影响因子：
--
作者：
Drusco A;Bottoni A;Laganà A;Acunzo M;Fassan M;Cascione L;Antenucci A;Kumchala P;Vicentini C;Gardiman MP;Alder H;Carosi MA;Ammirati M;Gherardi S;Luscrì M;Carapella C;Zanesi N;Croce CM
通讯作者：
Croce CM
影响因子：
6
作者：
Flannery, T;Gibson, D;Johnston, PG
通讯作者：
Johnston, PG