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Immunomodulatory effect of captopril and local irradiation on myeloid-derived suppressor cells
Radiation Oncology Journal ; : 223-229, 2016.
Article in English | WPRIM | ID: wpr-39692
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.
Subject(s)

Full text: Available Index: WPRIM (Western Pacific) Main subject: Radiotherapy / Triacetoneamine-N-Oxyl / Angiotensin-Converting Enzyme Inhibitors / Captopril / Random Allocation / Vascular Endothelial Growth Factor A / Hypoxia-Inducible Factor 1 / Flow Cytometry / Injections, Intraperitoneal / Leg Type of study: Prognostic study Limits: Animals Language: English Journal: Radiation Oncology Journal Year: 2016 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Radiotherapy / Triacetoneamine-N-Oxyl / Angiotensin-Converting Enzyme Inhibitors / Captopril / Random Allocation / Vascular Endothelial Growth Factor A / Hypoxia-Inducible Factor 1 / Flow Cytometry / Injections, Intraperitoneal / Leg Type of study: Prognostic study Limits: Animals Language: English Journal: Radiation Oncology Journal Year: 2016 Type: Article