Repository logo
  • English
  • 中文
Log In
Have you forgotten your password?
  1. Home
  2. College of Medicine / 醫學院
  3. Oncology / 腫瘤醫學研究所
  4. Cabozantinib is selectively cytotoxic in acute myeloid leukemia cells with FLT3-internal tandem duplication (FLT3-ITD)
 
  • Details

Cabozantinib is selectively cytotoxic in acute myeloid leukemia cells with FLT3-internal tandem duplication (FLT3-ITD)

Journal
Cancer Letters
Journal Volume
376
Journal Issue
2
Pages
218
Date Issued
2016
Author(s)
Lu J.-W
Wang A.-N
Liao H.-A
Chen, Chien-Yuan  
HSIN-AN HOU  
CHUNG-YI HU  
HWEI-FANG TIEN  
DA-LIANG OU  
LIANG-IN LIN  
DOI
10.1016/j.canlet.2016.04.004
URI
https://www.scopus.com/inward/record.uri?eid=2-s2.0-84962751661&doi=10.1016%2fj.canlet.2016.04.004&partnerID=40&md5=86d47fbb050b364036d331bedafd4cd2
https://scholars.lib.ntu.edu.tw/handle/123456789/508513
http://ntur.lib.ntu.edu.tw//handle/246246/280861
Abstract
Cabozantinib is an oral multikinase inhibitor that exhibits anti-tumor activity in several cancers. We found that cabozantinib was significantly cytotoxic to MV4-11 and Molm-13 cells that harbored FLT3-ITD, resulting in IC50 values of 2.4 nM and 2.0 nM, respectively. However, K562, OCI-AML3 and THP-1 (leukemia cell lines lacking FLT3-ITD) were resistant to cabozantinib, showing IC50 values in the micromolar range. Cabozantinib arrested MV4-11 cell growth at the G0/G1 phase within 24 h, which was associated with decreased phosphorylation of FLT3, STAT5, AKT and ERK. Additionally, cabozantinib induced MV4-11 cell apoptosis in a dose-dependent manner (as indicated by annexin V staining and high levels of cleaved caspase 3 and PARP-1), down-regulated the anti-apoptotic protein survivin and up-regulated the pro-apoptotic protein Bak. Thus, cabozantinib is selectively cytotoxic to leukemia cells with FLT3-ITD, causing cell-cycle arrest and apoptosis. In mouse xenograft model, cabozantinib significantly inhibited MV4-11 and Molm-13 tumor growth at a dosage of 10 mg/kg and showed longer survival rate. Clinical trials evaluating the efficacy of cabozantinib in acute myeloid leukemia (AML) with FLT3-ITD are warranted. ? 2016 Elsevier Ireland Ltd.
SDGs

[SDGs]SDG3

Other Subjects
cabozantinib; caspase 3; CD135 antigen; cyclin dependent kinase inhibitor; cyclin E; mitogen activated protein kinase; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1; protein Bak; protein kinase B; protein p27; STAT5 protein; survivin; anilide; antineoplastic agent; apoptosis regulatory protein; cabozantinib; CD135 antigen; FLT3 protein, human; protein kinase inhibitor; pyridine derivative; acute myeloblastic leukemia; animal cell; animal model; animal tissue; antineoplastic activity; antiproliferative activity; apoptosis; Article; cancer inhibition; cancer survival; cell cycle arrest; cell cycle S phase; cell proliferation; cell viability; controlled study; down regulation; drug cytotoxicity; drug efficacy; female; flow cytometry; G1 phase cell cycle checkpoint; human; human cell; immunohistochemistry; internal tandem duplication; leukemia cell; mouse; multiple cycle treatment; nonhuman; priority journal; protein cleavage; protein expression; protein phosphorylation; quantitative analysis; real time polymerase chain reaction; signal transduction; survival time; tandem repeat; tumor volume; upregulation; Western blotting; animal; antagonists and inhibitors; Bagg albino mouse; cell cycle checkpoint; dose response; drug effects; drug resistance; drug screening; enzymology; gene duplication; genetic predisposition; genetics; HL-60 cell line; K-562 cell line; Leukemia, Myeloid, Acute; metabolism; molecularly targeted therapy; nude mouse; pathology; phenotype; time factor; U-937 cell line; Anilides; Animals; Antineoplastic Agents; Apoptosis; Apoptosis Regulatory Proteins; Cell Cycle Checkpoints; Cell Proliferation; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Female; fms-Like Tyrosine Kinase 3; Gene Duplication; Genetic Predisposition to Disease; HL-60 Cells; Humans; K562 Cells; Leukemia, Myeloid, Acute; Mice, Inbred BALB C; Mice, Nude; Molecular Targeted Therapy; Phenotype; Protein Kinase Inhibitors; Pyridines; Signal Transduction; Time Factors; Tumor Burden; U937 Cells; Xenograft Model Antitumor Assays
Publisher
Elsevier Ireland Ltd
Type
journal article

臺大位居世界頂尖大學之列,為永久珍藏及向國際展現本校豐碩的研究成果及學術能量,圖書館整合機構典藏(NTUR)與學術庫(AH)不同功能平台,成為臺大學術典藏NTU scholars。期能整合研究能量、促進交流合作、保存學術產出、推廣研究成果。

To permanently archive and promote researcher profiles and scholarly works, Library integrates the services of “NTU Repository” with “Academic Hub” to form NTU Scholars.

總館學科館員 (Main Library)
醫學圖書館學科館員 (Medical Library)
社會科學院辜振甫紀念圖書館學科館員 (Social Sciences Library)

開放取用是從使用者角度提升資訊取用性的社會運動,應用在學術研究上是透過將研究著作公開供使用者自由取閱,以促進學術傳播及因應期刊訂購費用逐年攀升。同時可加速研究發展、提升研究影響力,NTU Scholars即為本校的開放取用典藏(OA Archive)平台。(點選深入了解OA)

  • 請確認所上傳的全文是原創的內容,若該文件包含部分內容的版權非匯入者所有,或由第三方贊助與合作完成,請確認該版權所有者及第三方同意提供此授權。
    Please represent that the submission is your original work, and that you have the right to grant the rights to upload.
  • 若欲上傳已出版的全文電子檔,可使用Open policy finder網站查詢,以確認出版單位之版權政策。
    Please use Open policy finder to find a summary of permissions that are normally given as part of each publisher's copyright transfer agreement.
  • 網站簡介 (Quickstart Guide)
  • 使用手冊 (Instruction Manual)
  • 線上預約服務 (Booking Service)
  • 方案一:臺灣大學計算機中心帳號登入
    (With C&INC Email Account)
  • 方案二:ORCID帳號登入 (With ORCID)
  • 方案一:定期更新ORCID者,以ID匯入 (Search for identifier (ORCID))
  • 方案二:自行建檔 (Default mode Submission)
  • 方案三:學科館員協助匯入 (Email worklist to subject librarians)

Built with DSpace-CRIS software - Extension maintained and optimized by 4Science