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  • [J Drug Target.] A new tyrosine kinase inhibitor K905-0266 inhibits proliferation and sphere formation of glioblastoma cancer cells.

    2020년 05월호
    [J Drug Target.] A new tyrosine kinase inhibitor K905-0266 inhibits proliferation and sphere formation of glioblastoma cancer cells.

    경북의대 / Senthilkumar Kalimuthu, 안병철*

  • 출처
    J Drug Target.
  • 등재일
    2020 Mar 19:1-19. doi: 10.1080/1061186X.2020.17458
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  • 내용

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    Abstract
    Glioblastoma (GBM) is the most prevalent malignant tumor of the central nervous system and carries a poor prognosis; average survival time after diagnosis is 14 months. Because of its unfavorable 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 characterized 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.

     

    K905-0266처리시 교모세포종세포의 sphere 형성이 억제됨을 보여줌.

     


    Author information

    Kalimuthu S1,2, Gangadaran P1,2,3, Oh JM1,2, Rajendran RL1,2,3, Lee HW1,2, Gopal A1,2, Hong CM1,2, Jeon YH4,5, Jeong SY1,2, Lee SW1,2, Lee J1,2, Ahn BC1,2,3.
    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 360-4, South Korea.
    5
    Leading-Edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu 702-210, South Korea.

  • 키워드
    Glioblastoma; Sphere formation; bioluminescent imaging; cancer stem cells; tyrosine kinase inhibitor
  • 연구소개
    종양치료에서 cancer stem cell의 사멸은 종양치료에 중요한 요소임. 본 연구는 교모세포종의 줄기세포에 새롭게 발견된 tyrosine kinase 억제제인 K905-0266가 억제효과가 있다는 것을 보여준 연구임. 해당 억제제는 phosphorylated ERK, Bcl-2를 감소시켜는 것으로 확인됨.
  • 편집위원

    Tyrosine Kinase 억제제인 K905-0266는 뇌교종세포의 암줄기세포의 특성 중 하나인 3-dimension 세포 배양시 sphere 형성을 억제함을 보여준 연구임. 악성종양의 완치를 위한 암줄기세포의 극복에 대한 연구로 종양관련 기초 연구자 및 임상가에게 관심을 유도할 연구로 생각됨.

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