MCCK1 enhances the anticancer effect of temozolomide in attenuating the invasion, migration and epithelial‐mesenchymal transition of glioblastoma cells in vitro and in vivo

Abstract

Abstract 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.

Keywords

• epithelial‐mesenchymal transition
• glioblastoma therapy
• IKKε inhibitor
• MCCK1
• temozolomide