Open AccessSuppression of HIF-1α expression and radiation resistance in acute hypoxic conditions
Author(s) -
Takahiro Oike,
Yoshiyuki Suzuki,
Wael S. Al-Jahdari,
A. Mobaraki,
Junichi Saitoh,
Kohta Torikai,
Katsuyuki Shirai,
Takashi Nakano
Publication year - 2011
Publication title -
experimental and therapeutic medicine
Language(s) - English
Resource type - Journals
eISSN - 1792-1015
pISSN - 1792-0981
DOI - 10.3892/etm.2011.373
Subject(s) - radioresistance , hypoxia (environmental) , oxygen enhancement ratio , tirapazamine , apoptosis , clonogenic assay , oncogene , a549 cell , cell cycle , cell culture , biology , cancer research , ionizing radiation , in vitro , andrology , microbiology and biotechnology , chemistry , cytotoxicity , medicine , oxygen , irradiation , biochemistry , genetics , physics , organic chemistry , nuclear physics
Recently, it has become clear that acute hypoxia affecting radioresistance exists widely in tumor tissues. Concurrently, hypoxia-inducible factor-1α (HIF-1α) is recognized as an essential transcriptional factor, enabling cells to survive through hypoxia. However, it is unclear as to whether HIF-1α plays a direct role in the radioresistance caused by acute hypoxia. Therefore, in this study, we investigated the in vitro response of the human lung adenocarcinoma cell line, A549, to ionizing radiation in an experimental model that imitates acute hypoxia in the presence and absence of HIF-1α expression, using the HIF-1α inhibitor 5-[1-(phenylmethyl)-1H-indazol-3-yl]-2-furanmethanol (YC-1). Cells were treated with or without 10 μM YC-1 for 2 h. Cells were exposed to either 95% N(2) and 5% CO(2) (hypoxic condition of <0.1 mmHg) or atmospheric air (normoxic condition) for 1 h, and irradiated with 2, 5 and 10 Gy. Western blot analysis revealed that, without YC-1, cells exposed to hypoxic conditions expressed increased levels of HIF-1α compared with those exposed to normoxic conditions. Under hypoxic conditions, HIF-1α expression was suppressed by YC-1 to the same extent as that observed in cells exposed to normoxic conditions without YC-1. Clonogenic survival assay revealed that under hypoxic conditions there was no significant difference between the surviving fraction of cells treated with YC-1 and without YC-1 at any dose point examined. The oxygen enhancement ratio at 10% surviving fraction was calculated as 2.7 and 2.6 in the presence and the absence of YC-1, respectively. These results indicate that HIF-1α itself is not an immediate cause of acute hypoxia-induced radioresistance in A549 cells.