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

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.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Chen Y,Lee CH,Tseng BY,Tsai YH,Tsai HW,Yao CL,Tseng SH

doi

10.21873/anticanres.12369

subject

Has Abstract

pub_date

2018-03-01 00:00:00

pages

1445-1454

issue

3

eissn

0250-7005

issn

1791-7530

pii

38/3/1445

journal_volume

38

pub_type

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