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https://ir.cnu.edu.tw/handle/310902800/32548
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| 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
mTORC1/2
AZD2014 |
| 日期: | 2019-09 |
| 上傳時間: | 2020-07-29 13:49:25 (UTC+8) |
| 出版者: | INT INST ANTICANCER RESEARCH |
| 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 |
| 顯示於類別: | [藥學系(所)] 期刊論文
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