mTORC1/2 Inhibitor Served as a More Ideal Agent Against the Growth of Mouse Lymphocytic Leukemia Both In Vitro and In Vivo

doi:10.21873/anticanres.13668

CNU IR > Pharmacy and Science > Dept. of Pharmacy > Periodical Articles > Item 310902800/32548

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Title:	mTORC1/2 Inhibitor Served as a More Ideal Agent Against the Growth of Mouse Lymphocytic Leukemia Both In Vitro and In Vivo
Authors:	Liao, Hui-Fen Lin, You-Zhu Yu, Chih-Chia Tai, Tzong-Shyuan Hung, Shih-Kai Ching-Chieh Yang(楊清傑) Su, Yu-Chieh
Contributors:	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
Keywords:	Chronic lymphocytic leukemia mammalian target of rapamycin mTORC1/2 AZD2014
Date:	2019-09
Issue Date:	2020-07-29 13:49:25 (UTC+8)
Publisher:	INT INST ANTICANCER RESEARCH
Abstract:	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.
Relation:	Anticancer Research, v.39, n.9, pp.4829-4835
Appears in Collections:	[Dept. of Pharmacy] Periodical Articles

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