HIF-1α and Resistance to Ionizing Radiation in Rectal Cancer
- *Corresponding Author:
- Sergio Huerta, MD, FACS
VA North Texas Health Care System
Department of Surgery (112)
4500 S. Lancaster Road, Dallas, TX 75216, USA
E-mail: [email protected]
Received date: June 05, 2014; Accepted date: July 16, 2014; Published date: July 18, 2014
Citation: Harris K, Gao X, Huerta-Yepez S, Kapur P, Huerta S (2014) HIF-1a and Resistance to Ionizing Radiation in Rectal Cancer. Surgery Curr Res 4:200. doi:10.4172/2161-1076.1000200
Copyright: © 2014 Harris K, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Introduction: There is a wide range of responses to pre-operative chemoradiation (CRT) in patients with rectal cancer. Factors that dictate tumors response have not been identified. The objective of this study was to determine the role of hypoxia-inducible factor 1-alpha (HIF-1α) in in vitro and ex vivo models of rectal cancer.
Methods: Levels of HIF-1α were assessed in radiosensitive (HCT-116) and a radioresistant (HT-29) cells. Radioresistant HT-29 cells were exposed to a potent radiosensitizing agent (a nitric oxide donor: DETANONOate [1 mM]) and IR followed by Western blot analysis with anti- HIF-1α antibodies. Patients with rectal cancer that were treated with CRT were separated based on good responders (≥ 50% reduction in tumor by comparing tumor size pre-operatively and postoperatively) compared to those that did not respond (<50% reduction in tumor). Blocks were stained for HIF-1α. Tissues collected from normal colonic epithelium from all these patients were subjected to the same treatments.
Results: In vitro, radiosensitive HCT-116 colorectal cancer cells demonstrated low levels of HIF-1α following treatment IR. Western blot analysis showed high protein levels of HIF-1α in radioresistant HT-29 cells subjected to IR with induction at 2.0 and 4.0 Gy. Protein levels of HIF-1α were attenuated by treatment of cells HT-29 with the radiosensitizing agent DETANONOate following exposure to IR. Ex vivo, tissue microarrays demonstrated no difference in HIF-1α expression between patients with a poor response to CRT (418.1 ± 32.6) vs. good responders (371.1 ± 31.5; p=0.3). However, examination tumor tissue compared to normal epithelium showed an increase in HIF-1α (1.5 fold; p<0.001) in patients who responded poorly to IR. This effect was not observed in the cohort of patients who responded well to IR.
Conclusions: The results of this study further support the potential role of HIF-1α in resistance to IR. This study implicates it a potential role of HIF-1α in rectal cancers.