|
KMID : 1038620160340030223
|
|
Radiation Oncology Journal
2016 Volume.34 No. 3 p.223 ~ p.229
|
|
|
Immunomodulatory effect of captopril and local irradiation on myeloid-derived suppressor cells
|
|
Cho Won-Kyung
Shin Sung-Won
Kim Shin-Yeong
Hong Chang-Won
Choi Chang-Hoon
Park Won
Noh Jae-Myoung
|
|
|
Abstract
|
|
|
Purpose: This study is to investigate the effect of captopril when combined with irradiation.
Materials and Methods: 4T1 (mouse mammary carcinoma) cells were injected in the right hind leg of Balb/c mice. Mice were randomized to four groups; control (group 1), captopril-treated (group 2), irradiated (group 3), irradiated and captopril-treated concurrently (group 4). Captopril was administered by intraperitoneal injection (10 mg/kg) daily and irradiation was delivered on the tumor-bearing leg for 15 Gy in 3 fractions. Surface markers of splenic neutrophils (G-MDSCs) and intratumoral neutrophils (tumor-associated neutrophils [TANs]) were assessed using flow cytometry and expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 alpha (HIF-1α) of tumor was evaluated by immunohistochemical (IHC) staining.
Results: The mean tumor volumes (±standard error) at the 15th day after randomization were 1,382.0 (±201.2) mm3 (group 1), 559.9 (±67.8) mm3 (group 3), and 370.5 (± 48.1) mm3 (group 4), respectively. For G-MDSCs, irradiation reversed decreased expression of CD101 from tumor-bearing mice, and additional increase of CD101 expression was induced by captopril administration. Similar tendency was observed in TANs. The expression of tumor-necrosis factor-associated molecules, CD120 and CD137, are increased by irradiation in both G-MDSCs and TANs. Further increment was observed by captopril except CD120 in TANs. For IHC staining, VEGF and HIF-1α positivity in tumor cells were decreased when treated with captopril.
Conclusion: Captopril is suggested to have additional effect when combined to irradiation in a murine tumor model by modulation of MDSCs and angiogenesis.
|
|
|
KEYWORD
|
|
|
Radiotherapy, Angiotensin converting enzyme inhibitors, Neutrophil
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|
|