Immunomodulatory effect of captopril and local irradiation on myeloid-derived suppressor cells.
- Author:
Won Kyung CHO
1
;
Sung Won SHIN
;
Shin Yeong KIM
;
Chang Won HONG
;
Changhoon CHOI
;
Won PARK
;
Jae Myoung NOH
Author Information
- Publication Type:Original Article
- Keywords: Radiotherapy; Angiotensin converting enzyme inhibitors; Neutrophil
- MeSH: Angiotensin-Converting Enzyme Inhibitors; Animals; Captopril*; Flow Cytometry; Hypoxia-Inducible Factor 1; Injections, Intraperitoneal; Leg; Mice; Neutrophils; Radiotherapy; Random Allocation; Triacetoneamine-N-Oxyl; Vascular Endothelial Growth Factor A
- From:Radiation Oncology Journal 2016;34(3):223-229
- CountryRepublic of Korea
- Language:English
- 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.
