LF-MF suppresses the colon cancer via regulating the function of MDSCs

Abstract

The biological effect of magnetic field is a hot topic in biomedical engineering. The influence of magnetic fields on human health has caused the widespread concern, involving the study of magnetic field in central nervous system, blood and immune system, vascular and endocrine system, among which the most attractive application is usage of low frequency magnetic fields (LF-MF) in the tumor treatment. Our previous studies showed that LF-MF significantly inhibited the proliferation of liver cancer, lung cancer and melanoma cells, and regulated the immune cells to exert anti-tumor effect. We have found that LF-MF exposure was associated with activation of macrophages and dendritic cells, enhanced profiles of CD4+ T and CD8+ T lymphocytes, the balance of Th17/Treg in tumor-bearing mice. In cancer, myeloid-derived suppressor cells (MDSCs) demonstrating one of the key players engaged in tumor immunosuppression. This study will further explore the role of LF-MF in the growth of colon cancer and function of myeloid-derived suppressor cells (MDSCs). In this study, mouse colon cancer xenografts models were established and the tumor-bearing mice were exposed to a LF-MF (0.4 T, 7.5 Hz) for 35 days. The tumor growth and tumor weight were measured. Immunohistochemical staining for Ki-67 in tumor tissue was performed. Flow cytometry analyzed the proportion of MDSCs in the bone marrow, spleen, tumor, and peripheral blood of mice. Magnetic beads separated MDSCs from tumor tissues and MDSCs suppression assays were performed. Q-PCR was performed to detect the mRNA expression of Arg-1 , iNOS-2 , Gp91 phox , P47phox , and S100A8/A9 in MDSCs from tumor tissues. The reactive oxygen species(ROS)level in MDSCs was analyzed by flow cytometry. Western blot was used to detect the protein level of Gp91phox, P47phox and GAPDH. Results showed that LF-MF inhibited the tumor growth in the CT26 colon cancer xenograft model, and decreased the number of Ki-67 positive cells in the tumor tissues. LF-MF reduced the proportion of MDSCs in tumor tissues and attenuated the inhibitory function of MDSCs. In vitro , LF-MF had no effect on cell viability and cell apoptosis of MDSCs. In addition, LF-MF reduced the production of reactive oxygen species in MDSCs by inhibiting the expression of Gp91phox and P47phox. With the reduced the production of reactive oxygen species, the inhibitory function of MDSCs was attenuated by LF-MF. Together, our present study demonstrated that LF-MF obviously suppressed the development of colon cancer via regulating the expansion and function of MDSCs. LF-MF suppressed the inhibitory function of MDSCs by reducing the production of reactive oxygen species with the decreased expression of Gp91phox and P47phox. Our studies reveal a novel mechanism behind the anti-tumor effect of LF-MFs on colon cancer and provide a potentially useful adjunct therapy for treatment of colon cancer.