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AT-406, an IAP inhibitor, activates apoptosis and induces radiosensitization of normoxic and hypoxic cervical cancer cells.

Abstract：

:IAP antagonists increased the antitumor efficacy of X-irradiation in some types of cancers, but their effects on hypoxic cancer cells remain unclarified. We aims to investigate the radiosensitizing effect of an IAP inhibitor AT-406 on cervical cancer cell lines under both normoxia and hypoxia conditions. Hela and Siha cells were treated to investigate the effects of drug administration on cell proliferation, apoptosis, and radiosensitivity. Western blot analysis was used to determine the role of AT-406 in inhibition of IAPs. The pathway of apoptosis was characterized by caspases activity assay. AT-406 potently sensitized Hela cells but not Siha cells to radiation under normoxia. Notably, the radiosensitizing effect of AT-406 on hypoxic cells was more evident than on normoxic cells in both cell lines. Further mechanism studies by western blot showed that under normoxia AT-406 decreased the level of cIAP1 in Hela cells in a dose-dependent manner; while additional downregulation of XIAP expression was induced by AT-406 treatment under hypoxia in both cell lines. Finally, AT-406 works on both extrinsic death receptor and intrinsic mitochondrial apoptosis pathways to activate apoptosis. Totally, AT-406 acts as a strong radiosensitizer in human cervical cancer cells, especially in hypoxic condition.

journal_name

J Pharmacol Sci

journal_title

Journal of pharmacological sciences

authors

Lu J,Qin Q,Zhan LL,Liu J,Zhu HC,Yang X,Zhang C,Xu LP,Liu ZM,Wang D,Cui HQ,Meng CC,Cai J,Cheng HY,Sun XC

doi

10.1254/jphs.14079fp

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

56-65

issue

1

eissn

1347-8613

issn

1347-8648

pii

DN/JST.JSTAGE/jphs/14079FP

journal_volume

126

pub_type

杂志文章

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