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    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/32548

    標題: mTORC1/2 Inhibitor Served as a More Ideal Agent Against the Growth of Mouse Lymphocytic Leukemia Both In Vitro and In Vivo
    作者: Liao, Hui-Fen
    Lin, You-Zhu
    Yu, Chih-Chia
    Tai, Tzong-Shyuan
    Hung, Shih-Kai
    Ching-Chieh Yang(楊清傑)
    Su, Yu-Chieh
    貢獻者: Natl Chiayi Univ, Dept Biochem Sci & Technol
    Dalin Tzu Chi Hosp, Buddhist Tzu Chi Med Fdn, Dept Radiat Oncol
    E Da Hosp, Dept Med Res
    Chi Mei Med Ctr, Dept Radiat Oncol
    Natl Sun Yat Sen Univ, Inst Biomed Sci
    Chia Nan Univ Pharm & Sci, Dept Pharm
    Kaohsiung Med Univ Hosp, Div Hematol Oncol, Dept Internal Med
    Kaohsiung Med Univ, Fac Med
    關鍵字: Chronic lymphocytic leukemia
    mammalian target of rapamycin
    日期: 2019-09
    上傳時間: 2020-07-29 13:49:25 (UTC+8)
    摘要: Background/Aim: Chronic lymphocytic leukemia (CLL) still remains an incurable disease as the cells evade apoptosis, which is an obstacle for current therapeutic approaches. Therefore, our aim was to identify an ideal target of leukemic cell growth for developing inhibitors. Materials and Methods: Mouse lymphocytic leukemia cell line L1210, human Toledo cells and a DBA/2 mouse graft model were used to analyze the activity of dual mTORC1/2 inhibitor AZD2014s. Western blotting and flow cytometry were performed to determine the mechanism. Results: AZD2014 inhibited L1210 and human Toledo cell proliferation. Treatment with AZD2014 reduced the phosphorylation levels of S6K1 and 4EBP1 and the protein levels of Rictor, a component of the mTORC2 pathway. AZD2014 induced cell cycle arrest at the G(0)-G(1) phase by reducing the expression of cyclin D1 and CDK4. Oral administration of AZD2014 significantly inhibited the growth of L1210 cell grafts in DBA/2 mice. Conclusion: The mTORC1/2 inhibitor may be a better therapeutic agent compared to PI3K/mTORC1 inhibitors for treating patients with CLL.
    關聯: Anticancer Research, v.39, n.9, pp.4829-4835
    Appears in Collections:[藥學系(所)] 期刊論文

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