title: Is the autophagy a friend or foe in the silver nanoparticles associated radiotherapy for glioma?
abstract: Malignant glioma is the most common intracranial tumor with a dismal prognosis. The radiosensitizing effect of silver nanoparticles (AgNPs) on glioma both in vitro and in vivo had been demonstrated in the previous studies of our group. However, the underlying mechanism is still unclear. Consistent with previous studies, a size and dose dependent antitumor effect and significant radiosensitivity enhancing effect of AgNPs were observed in our experiment system. We also found that cell protective autophagy could be induced by AgNPs and/or radiation, which was verified by the use of 3-MA. The mechanism through which had autophagy and the enhancement of radiosensitivity taken place was further investigated with inhibitors of ERK and JNK pathways. We demonstrated that ERK and JNK played pivotal roles in the radiosensitivity enhancement. Inhibiting ERK and JNK with U0126 and SP600125 respectively, we found that the autophagy level of the cells treated with AgNPs and radiation were attenuated. Moreover, SP600125 down-regulated the apoptosis rate of the co-treated cells significantly. Taken together, the present study would have important impact on biomedical applications of AgNPs and clinical treatment for glioma.
authors.affiliation: State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei 230027, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, PR China; Institute of Neurobiology, School of Medicine, Southeast University, Nanjing 210009, PR China.
authors.forename: Peidang
authors.initials: P
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, PR China.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Institute of Neurobiology, School of Medicine, Southeast University, Nanjing 210009, PR China.
authors.forename: Haizhen
authors.initials: H
authors.lastname: Jin
authors.affiliation: Tumor Center of Zhongda Hospital, Southeast University, Nanjing 210009, PR China.
authors.forename: Cailian
authors.initials: C
authors.lastname: Wang
authors.affiliation: Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei 230027, PR China. Electronic address: lpwen@ustc.edu.cn.
authors.forename: Longping
authors.initials: L
authors.lastname: Wen
authors.affiliation: State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, PR China. Electronic address: guning@seu.edu.cn.
authors.forename: Ning
authors.initials: N
authors.lastname: Gu
mesh_terms: D001343:Autophagy / Q000187:drug effects / Q000528:radiation effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D005910:Glioma / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry / Q000627:therapeutic use* / Q000648:ultrastructure; D010316:Particle Size; D011836:Radiation Tolerance / Q000187:drug effects; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000737:chemistry; D012834:Silver / Q000737:chemistry / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D011838:Radiation-Sensitizing Agents; D012834:Silver
keywords: Autophagy; Cell signaling pathways; Glioma; Radiation sensitization; Radiotherapy; Silver nanoparticles