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首页> 外文期刊>Chemotherapy Research and Practice >Inhibition of NF-κB by Dehydroxymethylepoxyquinomicin Suppresses Invasion and Synergistically Potentiates Temozolomide andγ-Radiation Cytotoxicity in Glioblastoma Cells
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Inhibition of NF-κB by Dehydroxymethylepoxyquinomicin Suppresses Invasion and Synergistically Potentiates Temozolomide andγ-Radiation Cytotoxicity in Glioblastoma Cells

机译：脱羟甲基环氧喹诺酮抑制NF-κB抑制胶质母细胞瘤细胞侵袭并协同增强替莫唑胺和γ辐射细胞毒性

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Despite advances in neurosurgery and aggressive treatment with temozolomide (TMZ) and radiation, the overall survival of patients with glioblastoma (GBM) remains poor. Vast evidence has indicated that the nuclear factor NF-κB is constitutively activated in cancer cells, playing key roles in growth and survival. Recently, Dehydroxymethylepoxyquinomicin (DHMEQ) has shown to be a selective NF-κB inhibitor with antiproliferative properties in GBM. In the present study, the ability of DHMEQ to surmount tumor's invasive nature and therapy resistance were further explored. Corroborating results showed that DHMEQ impaired cell growth in dose- and time-dependent manners with G2/M arrest when compared with control. Clonogenicity was also significantly diminished with increased apoptosis, though necrotic cell death was also observed at comparable levels. Notably, migration and invasion were inhibited accordingly with lowered expression of invasion-related genes. Moreover, concurrent combination with TMZ synergistically inhibited cell growth in all cell lines, as determined by proliferation and caspase-3 activation assays, though in those that express O6-methylguanine-DNA methyltransferase, the synergistic effects were schedule dependent. Pretreatment with DHMEQ equally sensitized cells to ionizing radiation. Taken together, our results strengthen the potential usefulness of DHMEQ in future therapeutic strategies for tumors that do not respond to conventional approaches.
机译：尽管神经外科手术和替莫唑胺（TMZ）和放射治疗取得了积极进展，但胶质母细胞瘤（GBM）患者的总体生存率仍然很差。大量证据表明，核因子NF-κB在癌细胞中被组成性激活，在生长和存活中起关键作用。最近，脱羟甲基环氧喹诺酮（DHMEQ）已显示是GBM中具有抗增殖特性的选择性NF-κB抑制剂。在本研究中，进一步探讨了DHMEQ克服肿瘤侵袭性和治疗抵抗力的能力。证实的结果表明，与对照相比，DHMEQ以剂量和时间依赖性方式破坏了细胞的生长，并导致G2 / M停滞。虽然在相当水平下也观察到坏死细胞死亡，但随着凋亡的增加，克隆形成性也显着降低。值得注意的是，迁移和侵袭被相应地抑制了侵袭相关基因的表达。而且，通过增殖和caspase-3活化试验确定，与TMZ并发联合可协同抑制所有细胞系中的细胞生长，尽管在表达O6-甲基鸟嘌呤-DNA甲基转移酶的试验中，协同作用是时间表依赖性的。 DHMEQ预处理可使细胞对电离辐射同样敏感。综上所述，我们的结果加强了DHMEQ在对常规方法无反应的肿瘤未来治疗策略中的潜在用途。

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