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

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.

• Authors: Tie Liu, Anqi Li, Yulun Xu, Yu Xin
• Journal: Cancer medicine (Cancer Med) Vol. 8 Issue 2 Pg. 751-760 (02 2019) ISSN: 2045-7634 [Electronic] United States
• PMID: 30656846 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Chemical References

• Antineoplastic Agents
• Rosaniline Dyes
• malachite green
• Temozolomide

Topics

• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Apoptosis (drug effects)
• Brain Neoplasms (drug therapy, pathology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Drug Synergism
• Epithelial-Mesenchymal Transition (drug effects)
• Female
• Glioblastoma (drug therapy, pathology)
• Humans
• Mice, Inbred BALB C
• Mice, Nude
• Rosaniline Dyes (pharmacology, therapeutic use)
• Temozolomide (pharmacology, therapeutic use)