A new tyrosine kinase inhibitor K905-0266 inhibits proliferation and sphere formation of glioblastoma cancer cells

Abstract

Glioblastoma (GBM) is the most prevalent malignant tumour of the central nervous system and carries a poor prognosis; average survival time after diagnosis is 14 months. Because of its unfavourable prognosis, novel therapies are needed. The aim of this study was to assess whether inhibition of GBM and GBM-derived cancer stem cells (CSCs) by a new tyrosine kinase inhibitor (TKI), K905-0266, is possible. To do this, we generated GBM (D54 and U87MG) cells expressing luciferase and characterised the inhibitory effects of the TKI with bioluminescent imaging (BLI) and western blot (WB). The effect of the TKI was then evaluated in CSCs. BLI showed significant inhibition of D54 and U87MG cells by TKI treatment. WB showed that the TKI decreased pERK and Bcl-2 level and increased cleaved caspase-3 level. Sphere formation was significantly reduced by the TKI in CSCs. Our results showed that a new TKI, K905-0266, effectively inhibited GBM and CSCs, making this a candidate for GBM therapy.

Keywords:

• Glioblastoma
• tyrosine kinase inhibitor
• cancer stem cells
• sphere formation
• bioluminescent imaging

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Basic Science Research Programme through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2016R1D1A1A02936968) and also by the National Research Foundation of Korea (NRF) grant funded by the Korea Government (2014R1A5A2009242).