Androgen deprivation modulates the inflammatory response induced by irradiation
1 Department of Urology, Chang Gung Memorial Hospital, Linko, Taiwan
2 Chang Gung University College of Medicine and Chang Gung Institute of Technology, Taiwan
3 Department of Radiation Oncology, Chang Gung Memorial Hospital, Chiayi, Taiwan
4 Department of Pathology, Chang Gung Memorial Hospital, Chiayi, Taiwan
BMC Cancer 2009, 9:92 doi:10.1186/1471-2407-9-92Published: 25 March 2009
The aim of this study was to determine whether radiation (RT)-induced inflammatory responses and organ damage might be modulated by androgen deprivation therapies.
The mRNA and tissue sections obtained from the lungs, intestines and livers of irradiated mice with or without androgen deprivation were analyzed by real-time PCR and histological analysis. Activation of NF-kappa B was examined by measuring nuclear protein levels in the intestine and lung 24 h after irradiation. We also examined the levels of cyclooxygenase-2 (COX-2), TGF-β1 and p-AKT to elucidate the related pathway responsible to irradiation (RT) -induced fibrosis.
We found androgen deprivation by castration significantly augmented RT-induced inflammation, associated with the increase NF-κB activation and COX-2 expression. However, administration of flutamide had no obvious effect on the radiation-induced inflammation response in the lung and intestine. These different responses were probably due to the increase of RT-induced NF-κB activation and COX-2 expression by castration or lupron treatment. In addition, our data suggest that TGF-β1 and the induced epithelial-mesenchymal transition (EMT) via the PI3K/Akt signaling pathway may contribute to RT-induced fibrosis.
When irradiation was given to patients with total androgen deprivation, the augmenting effects on the RT-induced inflammation and fibrosis should take into consideration for complications associated with radiotherapy.