Administration of granulocyte colony-stimulating factor with radiotherapy promotes tumor growth by stimulating vascularization in tumor-bearing mice

Kim,Joong Sun; Son,Yeonghoon; Bae,Min Ji; Lee,Minyoung; Lee,Chang Geun; Jo,Wol Soon; Kim,Sung Dae; Yang,Kwangmo

doi:10.3892/or.2015.3977

Administration of granulocyte colony-stimulating factor with radiotherapy promotes tumor growth by stimulating vascularization in tumor-bearing mice

Authors:
- Joong Sun Kim
- Yeonghoon Son
- Min Ji Bae
- Minyoung Lee
- Chang Geun Lee
- Wol Soon Jo
- Sung Dae Kim
- Kwangmo Yang
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Affiliations: Research Center, Dongnam Institute of Radiological and Medical Sciences (DIRAMS), Busan 619-953, Republic of Korea, College of Pharmacy, Kyungpook National University, Daegu 702-701, Republic of Korea
Published online on: May 13, 2015 https://doi.org/10.3892/or.2015.3977
Pages: 147-154

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Abstract

Although granulocyte-colony stimulating factor (G-CSF) is commonly used to support recovery from radiation-induced side-effects, the precise effects of G-CSF on colon cancer under radiotherapy remain poorly understood. In the present study, to investigate the effects of tumor growth following radiotherapy and G-CSF administration in a murine xenograft model of colon cancer, female BALB/c mice were injected with cells of a colon carcinoma cell line (CT26) with irradiation and G-CSF, alone or in combination. Mice received 2 Gy of focal radiation daily for 5 days and intraperitoneal injection of G-CSF (100 µg/kg/day) after irradiation for 7 days. Changes in the levels of myeloperoxidase (MPO), vascular endothelial growth factor (VEGF), matrix metalloproteinase type 9 (MMP-9) and CD31 were assessed in the mouse cancer induced by injection of colon cancer cells. We observed that G-CSF increased the number of circulating neutrophils, but facilitated tumor growth. However, G-CSF treatment did not affect radiation-induced cytotoxicity and cell viability in CT26 cells in vitro. Increased levels of myeloperoxidase, a neutrophil marker and those of vascular endothelial growth factor were observed in tumors with G-CSF supplementation. In addition, we found that increased levels of CD31 and matrix metalloproteinase-9 were correlated with the enhanced tumor growth after G-CSF treatment. Therefore, these data suggest that G-CSF may contribute to tumor growth and decrease the antitumor effect of radiotherapy, possibly by promoting vascularization in cancer lesions.

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