Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Cancer Med. 2019 Feb;8(2):751-760. doi: 10.1002/cam4.1951. Epub 2019 Jan 18.
Chemotherapy with temozolomide (TMZ) is the traditional treatment for glioblastoma (GBM). Nevertheless, majority of GBM patients have recurrence from resistance to the chemotherapy. Herein, we examined combinational effects of MCCK1 (a specific and effective IKKε inhibitor) with TMZ in GBM U251MG and U-87MG cell lines as well as U251MG xenograft models to overcome the therapeutic limitation of chemotherapy for GBM. Although MCCK1 alone showed inhibitory effects on in vitro proliferation, migration, invasion, and EMT of U251MG and U-87MG cells, combination of MCCK1 and TMZ showed enhanced inhibitory effects. In the U251MG GBM xenograft models, MCCK1 showed synergistic therapeutic effects in combination with TMZ to reduce tumor volumes significantly. These data indicated that MCCK1 could be a candidate sensitizer to potentiate therapeutic effects of conventional cytotoxic treatment for GBM.
替莫唑胺（TMZ）化疗是胶质母细胞瘤（GBM）的传统治疗方法。然而，大多数 GBM 患者对化疗有耐药性，导致复发。在此，我们研究了 MCCK1（一种特异性和有效的 IKKε 抑制剂）与 TMZ 在 GBM U251MG 和 U-87MG 细胞系以及 U251MG 异种移植模型中的联合作用，以克服化疗治疗 GBM 的局限性。虽然 MCCK1 单独对 U251MG 和 U-87MG 细胞的体外增殖、迁移、侵袭和 EMT 有抑制作用，但 MCCK1 与 TMZ 的联合使用显示出增强的抑制作用。在 U251MG GBM 异种移植模型中，MCCK1 与 TMZ 联合使用具有协同治疗作用，可显著降低肿瘤体积。这些数据表明，MCCK1 可能是一种候选增敏剂，可增强传统细胞毒性治疗 GBM 的治疗效果。
