Effect Of Senescent Microenvironment Induced By Radiotherapy On The Invasion Of Recurrent Glioblastoma

Objective To study the effect of brain microenvironment changes induced by radiotherapy on the invasiveness of recurrent glioblastoma(GBM).Methods GBM is always inevitable recurrence,and often located in the area of previous radiotherapy.In view of the clinical correlation between radiotherapy and recurrent GBM,eight groups of human GBM cell lines were implanted into the brain of nude mice 48 hours after pre radio therapy(15Gy)to observe the growth rate of tumor cells and the survival time of mice.GL261 tumor cells were used to study the effect of autoimmunity on radiotherapy in nude mice and C57BL/6 mice.Half brain radiotherapy was used to eliminate the difference between whole brain radiotherapy and human local radiotherapy.We used navitoclax to clear the senescent cell induced by radiotherapy to observe the growth of tumor cells and the survival time of mice,so as to verify the hypothesis that senescent cell induced by radiotherapy can accelerate the invasion of tumor cells.Results The growth rate of the six cell lines(GBM 6,46,76,143,164,196)in the brain of pre irradiated nude mice was faster than that in the control group,and the survival time of nude mice was also significantly shortened.On the contrary,the growth rate of GBM 10,12 cells was slower than that of the control group,and the survival time of the nude mice was also significantly prolonged.The growth rate of GL261 tumor cells increased significantly after pre radiotherapy.Similarly,the growth rate of GL261 tumor cells in the brain of nude mice was faster than that of C57BL/6 mice.There was no difference between half brain pre radiotherapy and whole brain radiotherapy.After using navitoclax to eliminate the senescent cell induced by radiotherapy,the growth rate of tumor cells slowed down and the survival time of mice prolonged.Conclusion The changes of brain microenvironment induced by radiotherapy significantly affect the invasiveness of most recurrent GBM cell lines,which is mainly related to cell senescence induced by radiotherapy.Further research is needed to determine the mechanism of the effect of radiation-induced senescence on tumor invasiveness.For the treatment of GBM,there is no single treatment is absolutely effective,so the best treatment is individualized multi-mode combination therapy.