Gamma-radiated immunosuppressed tumor xenograft mice can be a new ideal model in cancer research

Abstract

Tumor xenograft models can create a high capacity to study human tumors and discover efficient therapeutic approaches. Here, we aimed to develop the gamma-radiated immunosuppressed (GIS) mice as a new kind of tumor xenograft model for biomedical studies. First, 144 mice were divided into the control and treated groups exposed by a medical Cobalt-60 apparatus in 3, 4, and 5\xa0Gy based on the system outputs. Then, 144 BALB/c mice were divided into four groups; healthy, xenograft, radiation, and radiation\u2009+\u2009xenograft groups. The animals in the xenograft and radiation\u2009+\u2009xenograft groups have subcutaneously received 3\u2009×\u200910 6 MCF-7 cells 24\xa0h post-radiation. On 3, 7, 14, and 21\xa0days after cell injection, the animals were sacrificed. Then, the blood samples and the spleen and tumor tissues were removed for the cellular and molecular analyses. The whole-body gamma radiation had a high immunosuppressive effect on the BALB/c mice from 1 to 21\xa0days post-radiation. The macroscopic and histopathological observations have proved that the created clusters tumor structure resulted in the xenograft breast tumor. There was a significant increase in tumor size after cell injection until the end of the study. Except for Treg, the spleen level of CD4, CD8, CD19, and Ly6G was significantly decreased in Xen\u2009+\u2009Rad compared to the Xen alone group on 3 and 7\xa0days. Unlike IL-4 and IL-10, the spleen level of TGF-β, INF-γ, IL-12, and IL-17 was considerably decreased in the Xen\u2009+\u2009Rad than the Xen alone group on 3 and 7\xa0days. The spleen expressions of the VEGF, Ki67, and Bax/Bcl-2 ratio were dramatically increased in the Xen\u2009+\u2009Rad group compared to the Xen alone on 3, 7, 14, and 21\xa0days. Our results could confirm a new tumor xenograft model via an efficient immune-suppressive potential of the whole-body gamma radiation in mice.