Inhibition of Ciliogenesis Enhances the Cellular Sensitivity to Temozolomide and Ionizing Radiation in Human Glioblastoma Cells  

作　　者：WEI Li MA Wei CAI Hui PENG Shao Peng TIAN Huan Bing WANG Ju Fang GAO Lan HE Jin Peng 

机构地区：[1]School of Life Sciences,Lanzhou University,Lanzhou 730000,Gansu,China [2]NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor,Gansu Provincial Hospital,Lanzhou 730000,Gansu,China [3]Key Laboratory of Space Radiobiology of Gansu Province&CAS Key Laboratory of Heavy Ion Radiation Biology and Medicine,Institute of Modern Physics,Chinese Academy of Sciences,Lanzhou 730000,Gansu,China [4]University of Chinese Academy of Sciences,Beijing 100049,China

出　　处：《Biomedical and Environmental Sciences》2022年第5期419-436,共18页生物医学与环境科学（英文版）

基　　金：supported by the National Natural Sciences Foundation of China[31870851 and 31471953];the Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences[2019PT320005];the Science and Technology Research Project of Gansu Province[145RTSA012 and 20JR5RA555];the Youth Innovation Promotion Association CAS[2021415]

摘　　要：Objective To investigate the function of primary cilia in regulating the cellular response to temozolomide(TMZ)and ionizing radiation(IR)in glioblastoma(GBM).Methods GBM cells were treated with TMZ or X-ray/carbon ion.The primary cilia were examined by immunostaining with Arl13 b andγ-tubulin,and the cellular resistance ability was measured by cell viability assay or survival fraction assay.Combining with cilia ablation by IFT88 depletion or chloral hydrate and induction by lithium chloride,the autophagy was measured by acridine orange staining assay.The DNA damage repair ability was estimated by the kinetic curve ofγH2 AX foci,and the DNAdependent protein kinase(DNA-PK)activation was detected by immunostaining assay.Results Primary cilia were frequently preserved in GBM,and the induction of ciliogenesis decreased cell proliferation.TMZ and IR promoted ciliogenesis in dose-and time-dependent manners,and the suppression of ciliogenesis significantly enhanced the cellular sensitivity to TMZ and IR.The inhibition of ciliogenesis elevated the lethal effects of TMZ and IR via the impairment of autophagy and DNA damage repair.The interference of ciliogenesis reduced DNA-PK activation,and the knockdown of DNA-PK led to cilium formation and elongation.Conclusion Primary cilia play a vital role in regulating the cellular sensitivity to TMZ and IR in GBM cells through mediating autophagy and DNA damage repair.

关 键 词：Primary cilia GLIOBLASTOMA Cellular sensitivity TEMOZOLOMIDE Ionizing radiation Autophagy DNA damage response DNA-PK 

分 类 号：R739.4[医药卫生—肿瘤]