Development of bio-selective strategies to radio-resistant tumor cells

Radiotherapy is one of the established treatments for solid tumors. Investigation of tumor radioresistance is important for future tumor radiotherapy. Biological bases on the resistance have not been fully understood. Recent studies have demonstrated that there is a small fraction in solid tumor which is highly resistant to ionizing radiation and the radioresistant tumor cells often expressed some stem cell markers. Resistance of tumors to both radiation and chemotherapeutic agents can be attributed to the features of the cancer stem cells. In the present study, we show that a human glioblastoma cell line A172 transiently becomes to ''stem cell-like appearance'' when cultured with non-serum media supplemented with the growth factors. The treated cells were found significantly resistant to X-rays compared with the cells cultured in normal media. Phosphorylation of histon H2Ax was induced in both forms, however, stem cell-like cells contained subpopulation which is more registant to IR than the parental A172 cells. Our result is consistent with the hypothesis that cancer stemness contribute to the radioresistance probably by their efficient repair activity on DNA double-strand breaks. (author)