Comparison of Radiocurability of Human Xenograft Tumor After Irradiated With Carbon-Ion and X-ray In Nude Mice

To determine xenograft tumor radiocurability of carbon-ion (C290, 50keV/m, 6-cm SOBP) and X-ray, human colon cancer cells HCT116 were inoculated into the nude mice and were irradiated when the tumors grew to a certain size. Carbon-ion irradiation effectively suppressed tumor growth. However, the tumors re-grew after 8-week when irradiated with 15 Gy, but all the tumors were regressed and consequently eradicated without any relapse in the 12-week follow-up when irradiated with 30 Gy. In comparison, xenograft tumors were suppressed for 4-week with 30 Gy and completely eradicated with 60 Gy X-ray irradiation. The relative biological effects (RBE) value of carbon-ion relative to X-rays was 3.82. At an isodose of 30 Gy, carbon-ion irradiation predominantly induced tumor cell cavitation, fiborosis and the duct-like architecture was completely disrupted, whereas X-ray irradiation only partially destroyed tumor cells and the duct-like architecture still remained. Histopathological analysis showed that tumor-supplying vessels were markedly reduced in carbon-ion irradiated mice compared to those of X-ray irradiated mice. Immunohistochemical study demonstrated that expression of VEGF, HIF-1, -catenin and cancer stem cell marker CD133 was predominantly suppressed by carbon-ion irradiation, whereas X-ray increased the expression of these proteins. In conclusion, heavy-ion irradiation has a high radiocurability compared to conventional X-ray. The effective suppression of tumor-induced angiogenesis and disruption of cancer stem cells are considered to be one of the crucial molecular mechanisms of heavy-ion radiotherapy.HEAVY IONS IN THERAPY AND SPACE SYMPOSIUM 200