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AZD8055 Exerts Antitumor Effects on Colon Cancer Cells by Inhibiting MTOR and Cell-cycle Progression

Overview
Journal Anticancer Res
Specialty Oncology
Date 2018 Mar 2
PMID 29491070
Citations 15
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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 G/G 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.

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