Heavy-Ion Irradiation Disrupts Cancer Stem Cells And Completely Controls Transplantable Human Colon Cancer In Nude Mice

Purpose: To clarify histopathological changes and molecular mechanisms of high LET heavy-ion radiation in the treatment of transplantable human colon cancer in Balb/c-nu/nu mice.Methods: HCT116 cells were inoculated into the mice and were irradiated with carbon-ion (C290, 50keV/microm, SOBP) or X-ray when the xenograft tumors grew to a certain size. Histopathological analysis and immunohistochemical study were carried out by the hematoxylin and eosin (HE) and avidin-biotin-peroxidase complex (ABC) methods.Results: Both X-rays (30Gy) and carbon-ion radiation (30Gy) effectively suppressed tumor growth. However, the tumors were re-grew in the X-ray irradiated mice after 4 weeks, in contrast, all the tumors were regressed and consequently the tumor size was remarkably decreased or completely disappeared without any relapse or re-growth. Tumor-supplying vessels were also reduced in carbon-ion irradiated mice compared to those of X-ray irradiated mice when examined one month later. Expression of vascular endothelial growth factor (VEGF), beta-catenin and cancer stem cell marker CD133+ was predominantly suppressed by carbon ion irradiation; by contrast, X-rays increased the expression of these proteins.Conclusions: Heavy-ion irradiation can radically control tumor growth compared to X-rays, and the suppression of tumor-induced angiogenesis and inhibition of cancer stem cells are considered as one of the most important molecular mechanisms of heavy ion radiotherapy.2nd Asian Congress of Radiation Researc