Anticancer research · 2016
Torin2 Potentiates Anticancer Effects on Adult T-Cell Leukemia/Lymphoma by Inhibiting Mammalian Target of Rapamycin.
Сравнительное исследованиеСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Watanabe Tatsuro, Sato Akemi, Kobayashi-Watanabe Naomi, Sueoka-Aragane Naoko, Kimura Shinya, Sueoka Eisaburo
Аннотация
BACKGROUND: Torin2 is a second-generation ATP-competitive inhibitor of the mammalian target of rapamycin (mTOR). Dysregulation of mTOR signaling pathway, consisting of mTOR complexes mTORC1 and mTORC2, is a promising therapeutic target in some human malignancies. We examined antitumor effects of Torin2 in adult T-cell leukemia/lymphoma (ATL)-related cell lines compared to those of rapamycin, a classical mTOR inhibitor.
MATERIALS AND METHODS: Cell growth was monitored by detecting viable cells with Cell Counting Kit-8 or trypan blue. Cell cycle was studied by flow cytometric analysis. The phosphorylation status of proteins in the mTOR signaling pathway was examined by western blot analysis.
RESULTS: Torin2 exhibited greater efficacy in cell growth inhibition than rapamycin, associated with a strong reduction of phosphorylated v-akt murine thymoma viral oncogene homolog (AKT) (Ser 473), that is downstream of mTORC2.
CONCLUSION: Since mTORC2 activates AKT, Torin2 might inhibit both mTORC1 and mTORC2, resulting in stronger growth inhibition of ATL cells.
MATERIALS AND METHODS: Cell growth was monitored by detecting viable cells with Cell Counting Kit-8 or trypan blue. Cell cycle was studied by flow cytometric analysis. The phosphorylation status of proteins in the mTOR signaling pathway was examined by western blot analysis.
RESULTS: Torin2 exhibited greater efficacy in cell growth inhibition than rapamycin, associated with a strong reduction of phosphorylated v-akt murine thymoma viral oncogene homolog (AKT) (Ser 473), that is downstream of mTORC2.
CONCLUSION: Since mTORC2 activates AKT, Torin2 might inhibit both mTORC1 and mTORC2, resulting in stronger growth inhibition of ATL cells.
Предметные рубрики MeSH
Antineoplastic AgentsApoptosisCell Line, TumorCell ProliferationCell SurvivalDose-Response Relationship, DrugEtoposideG1 Phase Cell Cycle CheckpointsHumansLeukemia-Lymphoma, Adult T-CellMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2Multiprotein ComplexesNaphthyridinesPhosphorylationProtein Kinase InhibitorsProto-Oncogene Proteins c-aktSignal TransductionSirolimusTOR Serine-Threonine Kinases