방사선의학 웹진

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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.

Affiliations

Senthilkumar Kalimuthu  1   2 , Prakash Gangadaran  1   2   3 , Ji Min Oh  1   2 , Ramya Lakshmi Rajendran  1   2   3 , Ho Won Lee  1   2 , Arunnehru Gopal  1   2 , Chae Moon Hong  1   2 , Yong Hyun Jeon  4   5 , Shin Young Jeong  1   2 , Sang-Woo Lee  1   2 , Jaetae Lee  1   2 , Byeong-Cheol Ahn  1   2   3
1 Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
2 Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea.
3 BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
4 Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, South Korea.
5 Leading‑Edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, South Korea.