Study On Host-derived Malignant Stroma Cells Which Induced By Glioma Stem Progenitor Cells Are More Resistant To Radiation

Objective: Malignant gliomas are the most common clinical primary brain tumors,and radiotherapy is one of the most important means of treatment. Studies have found that cancer stem cells are reasons for radioresistance of glioma. Glioma stem progenitor cells could induce malignant transformation of the host-derived cells in glioma stroma, however whether these malignant cells were resistant to radiation as glioma stem progenitor cells was still unknown. The molecular mechanisms underlying radioresistance of these cells deserved further investigation.Methods: The SU3-5R cells were the progeny of SU3 cells that had been irradiated with 4 Gy X-rays for 5 times to induce its radioresistance. CCK-8 assay for each cell line in vitro growth curves by comparing the growth and proliferation of cell lines. Clonogenic assays were performed to assess the radiosensitivity of SU3, SU3-5R and ih BTC2(transformed host glial cells induced by SU3), and the multi-target single-hit model was used to fit the survival curve. Quantitative Real Time-PCR was used to determine the relative m RNA levels of Notch1 and Hes1. p Akt and Bcl-2 protein levels were assayed by Western blot. Trypan blue staining method, chemiluminescence, flow cytometry analysis of apoptosis ih BTC2.Results: The host interstitial malignant transformed cells, ih BTC2, was more radioresistant than SU3 and SU3-5R. Proliferation of these cells was accelerated after radiation in vitro, radiation could upregulate p Akt activity and Bcl-2 expression levels in ih BTC2 cells. Notch inhibition with GSIs could sensitize radiation sensitivity of ih BTC2 cells.Conclusion: Notch signaling could be involved in radioresistance of ih BTC2 cells,which offered valuable references for further research on the role of tumor interstitial components in tumor radioresistance.