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Androgen deprivation modulates the inflammatory response induced by irradiation.

Wu CT, Chen WC, Lin PY, Liao SK, Chen MF - BMC Cancer (2009)

Bottom Line: We found androgen deprivation by castration significantly augmented RT-induced inflammation, associated with the increase NF-kappaB activation and COX-2 expression.However, administration of flutamide had no obvious effect on the radiation-induced inflammation response in the lung and intestine.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Urology, Chang Gung Memorial Hospital, Linko, Taiwan. chuntewu@adm.cgmh.org.tw

ABSTRACT

Background: The aim of this study was to determine whether radiation (RT)-induced inflammatory responses and organ damage might be modulated by androgen deprivation therapies.

Methods: 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-beta1 and p-AKT to elucidate the related pathway responsible to irradiation (RT) -induced fibrosis.

Results: We found androgen deprivation by castration significantly augmented RT-induced inflammation, associated with the increase NF-kappaB 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-kappaB activation and COX-2 expression by castration or lupron treatment. In addition, our data suggest that TGF-beta1 and the induced epithelial-mesenchymal transition (EMT) via the PI3K/Akt signaling pathway may contribute to RT-induced fibrosis.

Conclusion: 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.

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Representative picture for mice after castration.
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Figure 1: Representative picture for mice after castration.

Mentions: BALB/c mice were purchased from the National Science Council, Taiwan. A total of 60 male mice aged between 6 and 8 weeks old were used in this study. The protocol of animal experimentation was approved by the Chang Gung Memorial Hospital Experimental Animal Committee. For irradiation, anesthetized mice were restrained in modified Perspex tubes and received 20 Gy total body irradiation by 6 MV X-rays from a linear accelerator. Unirradiated mice were subjected to the same conditions but were not exposed to the radiation source (sham-irradiation). For androgen deprivation treatment, the mice were divided into three groups: 1. C-mice, the mice without any androgen deprivation treatment; 2. F-mice, the mice with flutamide administration (the mice were injected twice intraperitoneally with flutamide (1 mg/g dissolved in DMSO), 12 h before irradiation and 2 h after irradiation); 3. S-mice, the mice receive androgen deprivation treatment by surgical castration (Figure 1). In addition, TGF-β1 has a central role in modulation of immune reaction. We proposed TGF-β1 contributed to the RT-induced fibrosis via the PI3K/Akt signaling pathways. To test the hypothesis, the mice were injected intraperitoneally with 200 ng TGF-β1 for 3 days before following experiments or treated with Wortmannin, a PI3K/Akt inhibitor (0.1 mM in DMSO), 12 h before irradiation.


Androgen deprivation modulates the inflammatory response induced by irradiation.

Wu CT, Chen WC, Lin PY, Liao SK, Chen MF - BMC Cancer (2009)

Representative picture for mice after castration.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2667536&req=5

Figure 1: Representative picture for mice after castration.
Mentions: BALB/c mice were purchased from the National Science Council, Taiwan. A total of 60 male mice aged between 6 and 8 weeks old were used in this study. The protocol of animal experimentation was approved by the Chang Gung Memorial Hospital Experimental Animal Committee. For irradiation, anesthetized mice were restrained in modified Perspex tubes and received 20 Gy total body irradiation by 6 MV X-rays from a linear accelerator. Unirradiated mice were subjected to the same conditions but were not exposed to the radiation source (sham-irradiation). For androgen deprivation treatment, the mice were divided into three groups: 1. C-mice, the mice without any androgen deprivation treatment; 2. F-mice, the mice with flutamide administration (the mice were injected twice intraperitoneally with flutamide (1 mg/g dissolved in DMSO), 12 h before irradiation and 2 h after irradiation); 3. S-mice, the mice receive androgen deprivation treatment by surgical castration (Figure 1). In addition, TGF-β1 has a central role in modulation of immune reaction. We proposed TGF-β1 contributed to the RT-induced fibrosis via the PI3K/Akt signaling pathways. To test the hypothesis, the mice were injected intraperitoneally with 200 ng TGF-β1 for 3 days before following experiments or treated with Wortmannin, a PI3K/Akt inhibitor (0.1 mM in DMSO), 12 h before irradiation.

Bottom Line: We found androgen deprivation by castration significantly augmented RT-induced inflammation, associated with the increase NF-kappaB activation and COX-2 expression.However, administration of flutamide had no obvious effect on the radiation-induced inflammation response in the lung and intestine.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Urology, Chang Gung Memorial Hospital, Linko, Taiwan. chuntewu@adm.cgmh.org.tw

ABSTRACT

Background: The aim of this study was to determine whether radiation (RT)-induced inflammatory responses and organ damage might be modulated by androgen deprivation therapies.

Methods: 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-beta1 and p-AKT to elucidate the related pathway responsible to irradiation (RT) -induced fibrosis.

Results: We found androgen deprivation by castration significantly augmented RT-induced inflammation, associated with the increase NF-kappaB 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-kappaB activation and COX-2 expression by castration or lupron treatment. In addition, our data suggest that TGF-beta1 and the induced epithelial-mesenchymal transition (EMT) via the PI3K/Akt signaling pathway may contribute to RT-induced fibrosis.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus