https://scholars.lib.ntu.edu.tw/handle/123456789/476125
標題: | AZD8055 exerts antitumor effects on colon cancer cells by inhibiting mTOR and cell-cycle progression | 作者: | Chen Y. Lee C.-H. Tseng B.-Y. Tsai Y.-H. Tsai H.-W. Yao C.-L. SHENG-HONG TSENG |
關鍵字: | Apoptosis; AZD8055; Cell cycle; Colon cancer; MTOR | 公開日期: | 2018 | 出版社: | International Institute of Anticancer Research | 卷: | 38 | 期: | 3 | 起(迄)頁: | 1445-1454 | 來源出版物: | Anticancer Research | 摘要: | 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. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85043420383&doi=10.21873%2fanticanres.12369&partnerID=40&md5=99b3f43255f9fbe9b90e02f833927f17 https://scholars.lib.ntu.edu.tw/handle/123456789/476125 |
ISSN: | 0250-7005 | DOI: | 10.21873/anticanres.12369 | SDG/關鍵字: | 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 |
顯示於: | 醫學系 |
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