Carbon ion irradiation conquers the radioresistance by inducing complex DNA damage and apoptosis in U251 human glioblastomas cells.

Abstract

Glioblastoma multiforme (GBM) is the most malignant brain tumor, with radiotherapy frequently employed following surgical resection. However, conventional radiation therapies often yield suboptimal results. This study investigated the effects of X-ray and carbon ion irradiation on the glioblastoma cell line U251 to assess the distinctive advantages of carbon ion treatment and explore mechanisms for overcoming radiation resistance. The findings indicated that carbon ion irradiation more effectively inhibited colony formation and induced more severe apoptosis and cell cycle disorder in U251 cells. Immunofluorescence assays revealed larger and more abundant ϒ-H2AX and 53BP1 foci in the carbon ion irradiation group. Western blot analysis demonstrated that carbon ion-induced DNA damage repair involved a complex array of pathways, with the RAD51-mediated homologous recombination (HR) pathway being predominant, while the Rad23B-mediated nucleotide excision repair (NER) pathway and XRCC1-mediated base excision repair (BER) were more relevant in response to X-ray irradiation. These results suggest that carbon ion irradiation may overcome radioresistance by inducing more complex DNA damage and apoptosis, thus providing insights for targeting new strategies in combining gene therapy with radiotherapy.