Radiation Oncology Journal

The Korean Society for Radiation Oncology (대한방사선종양학회)
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Immunomodulatory effect of captopril and local irradiation on myeloid-derived suppressor cells

  • Cho, Won Kyung (Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Shin, Sung-Won (Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Shin-Yeong (Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Hong, Chang-Won (Department of Physiology, Kyungpook National University School of Medicine) ;
  • Choi, Changhoon (Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Park, Won (Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Noh, Jae Myoung (Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • Received : 2016.06.02
  • Accepted : 2016.07.12
  • Published : 2016.09.30
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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 ($HIF-1{\alpha}$) of tumor was evaluated by immunohistochemical (IHC) staining. Results: The mean tumor volumes (${\pm}$standard error) at the 15th day after randomization were $1,382.0({\pm}201.2)mm^3$ (group 1), $559.9({\pm}67.8)mm^3$ (group 3), and $370.5({\pm}48.1)mm^3$ (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 $HIF-1{\alpha}$ 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.

Keywords

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