AZD8055 exerts antitumor effects on colon cancer cells by inhibiting mTOR and cell-cycle progression
Journal
Anticancer Research
Journal Volume
38
Journal Issue
3
Pages
1445-1454
Date Issued
2018
Author(s)
Chen Y.
Lee C.-H.
Tseng B.-Y.
Tsai Y.-H.
Tsai H.-W.
Yao C.-L.
SHENG-HONG TSENG
Abstract
Background/Aim: AZD8055 is an inhibitor of mammalian target of rapamycin (mTOR) that can suppress both mTOR complex 1 (mTORC1) and mTORC2. This study investigated the antitumor effects of AZD8055 on colon cancer. Materials and Methods: The effects of AZD8055 on proliferation, apoptosis, and cell cycle of colon cancer cells, and tumor growth in a mouse colon cancer model were studied. Results: AZD8055 significantly inhibited proliferation and induced apoptosis of colon cancer cells (p<0.05). The phosphorylation of both AKT and S6 kinase 1 (S6K1) was suppressed by AZD8055. AZD8055 also induced G0/G1 cell-cycle arrest, reduced cyclin D1 and increased p27 expression, and suppressed the levels of phospho-cyclin-dependent kinase 2 and phospho-retinoblastoma. Compared to the control, oral administration of AZD8055 significantly suppressed tumor growth in mice (p<0.05). Conclusion: AZD8055 induces cytotoxicity, apoptosis, and cell-cycle arrest of colon cancer cells, and exerts an antitumor effect in mice. It also inhibits the mTOR signaling pathway and mTOR-dependent cell-cycle progression. ? 2018 International Institute of Anticancer Research. All rights reserved.
Subjects
Apoptosis; AZD8055; Cell cycle; Colon cancer; MTOR
SDGs
Other Subjects
azd 8055; cyclin D1; cyclin dependent kinase 2; mammalian target of rapamycin; protein kinase B; protein p27; retinoblastoma protein; S6 kinase; S6 kinase 1; unclassified drug; (5-(2,4-bis((3S)-3-methylmorpholin-4-yl)pyrido(2,3-d)pyrimidin-7-yl)-2-methoxyphenyl)methanol; morpholine derivative; target of rapamycin kinase; animal experiment; animal model; antineoplastic activity; apoptosis; Article; cancer inhibition; cell cycle G0 phase; cell cycle progression; cell proliferation; cell viability; colon cancer; controlled study; down regulation; drug cytotoxicity; enzyme inhibition; enzyme phosphorylation; G1 phase cell cycle checkpoint; HCT 116 cell line; HCT 15 cell line; human; human cell; in vitro study; LC50; male; mouse; mTOR signaling; nonhuman; priority journal; protein expression; upregulation; animal; antagonists and inhibitors; Bagg albino mouse; cell survival; colon tumor; drug effects; experimental neoplasm; metabolism; pathology; signal transduction; tumor cell line; tumor volume; Animals; Apoptosis; Cell Line, Tumor; Cell Proliferation; Cell Survival; Colonic Neoplasms; G1 Phase Cell Cycle Checkpoints; HCT116 Cells; Humans; Male; Mice, Inbred BALB C; Morpholines; Neoplasms, Experimental; Signal Transduction; TOR Serine-Threonine Kinases; Tumor Burden
Publisher
International Institute of Anticancer Research
Type
journal article