Radiat Oncol J.  2016 Sep;34(3):223-229. 10.3857/roj.2016.01816.

Immunomodulatory effect of captopril and local irradiation on myeloid-derived suppressor cells

• Cho WK
• Shin SW
• Kim SY
• Hong CW
• Choi C
• Park W
• Noh JM

• KMID: 2356119
• DOI: http://doi.org/10.3857/roj.2016.01816

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

MeSH Terms

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
Angiotensin-Converting Enzyme Inhibitors
Captopril
Hypoxia-Inducible Factor 1
Triacetoneamine-N-Oxyl
Vascular Endothelial Growth Factor A