Amentoflavone Effectively Blocked the Tumor Progression of Glioblastoma via Suppression of ERK/NF-κB Signaling Pathway
Amentoflavone Effectively Blocked the Tumor Progression of Glioblastoma via Suppression of ERK/NF-κB Signaling Pathway
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DOI：
10.1142/s0192415x19500484
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发表时间：
2019-01-01
影响因子：
5.7
通讯作者：
Chung, Jing-Gung
中科院分区：
文献类型：
--
作者：
Hsu, Fei-Ting;Chiang, I-Tsang;Chung, Jing-Gung
胶质母细胞瘤是中枢神经系统最常见的原发性恶性肿瘤，年发病率为5.26/10万人。标准治疗的临床结果和存活率仍然很差;因此，需要一种新的策略来治疗这种致命疾病。虽然已知穗花杉双黄酮在各种类型的癌症中具有抗癌潜力，但其抗胶质母细胞瘤的能力和机制仍不清楚。我们通过transwell实验证明穗花杉双黄酮可以抑制胶质母细胞瘤的侵袭和迁移。此外，我们还建立了NF-κ B报告基因系统，并利用该系统对穗花杉双黄酮的NF-κ B抑制作用进行了体内外研究。在此，我们指出穗花杉双黄酮不仅降低NF-κ B B活化，而且降低NF-κ B介导的下游癌基因的表达，如MMP-2，MMP-9，XIAP，cyclinD1和VEGF，这通过Western blot和免疫组织化学（IHC）来阐明。在穗花杉双黄酮治疗组中发现了肿瘤生长抑制和NF-κ B减少，这是由具有胶质母细胞瘤的动物模型揭示的。在本研究中，我们还使用ERK抑制剂和NF-κ B抑制剂（QNZ）来证实穗花杉双黄酮对胶质母细胞瘤的有益结果是否主要通过阻断ERK/NF-κ B信号传导来调节。综上所述，ERK/NF-κ B信号通路在穗花杉双黄酮抑制胶质母细胞瘤生长中具有一定作用。
Glioblastoma is the most common primary malignant tumor of the central nervous system, with an annual incidence of 5.26 per 100000 people. The clinical outcome of standard therapy and the survival rate remain poor; therefore, there is an unmet need for a new strategy to treat this lethal disease. Although amentoflavone was known to have anti-cancer potential in various types of cancers, its antiglioblastoma ability and mechanism remain unrecognized. We demonstrated that amentoflavone may suppress glioblastoma invasion and migration by transwell assay. Moreover, we established NF-kappa B reporter gene system and used that for verifying NF-kappa B inhibition efficacy of amentoflavone on in vitro and in vivo studies. Here, we indicated that amentoflavone not only diminished NF-kappa B activation, but also reduced NF-kappa B-mediated downstream oncogenes expression, such as MMP-2, MMP-9, XIAP, cyclinD1 and VEGF, which was elucidated by Western blot and immunohistochemistry (IHC). Tumor growth inhibition and NF-kappa B reduction was found in the amentoflavone treatment group, which was revealed by the glioblastoma-bearing animal model. In this study, we also used ERK inhibitor and NF-kappa B inhibitor (QNZ) to confirm whether the beneficial result of amentoflavone on glioblastoma was mainly regulated by blockage of ERK/NF-kappa B signaling. In summary, ERK/NF-kappa B signaling pathway has a role in the inhibition of tumor growth by amentoflavone in glioblastoma.