Is the autophagy a friend or foe in the silver nanoparticles associated radiotherapy for glioma？ |
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| Institution: | 1. Department of Chemical & Biological Engineering, Northwestern University, Evanston, IL, USA;2. Department of Radiology, Northwestern University, Chicago, IL, USA;3. Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA;4. Department of Biomedical Engineering, Northwestern University, Chicago, IL, USA;5. Department of Electrical Engineering and Computer Science, Evanston, IL, USA;1. Key Laboratory of Functional Polymer Materials of the Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China;2. Collaborative Innovation Center of Chemical Science and Engineering, Nankai University, Tianjin 300071, China;3. Department of Radiology, Tianjin Hospital, Tianjin 300210, China;1. Department of Medical Biomaterials Engineering, Kangwon National University, Chuncheon 200-701, Republic of Korea;2. Department of Chemistry, Kangwon National University, Chuncheon 200-701, Republic of Korea;3. Institute of Bioscience and Biotechnology, Kangwon National University, Republic of Korea;1. Osteoarticolar Regeneration Laboratory, Rizzoli Orthopaedic Institute, Bologna, Italy;2. Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum University of Bologna, Bologna, Italy;3. Cell Therapy Group, Institute for Advanced Chemistry of Catalonia (IQAC), CSIC, Barcelona, Spain;4. Networking Biomedical Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain;5. Laboratory of Immunorheumatology and Tissue Regeneration/RAMSES, Rizzoli Orthopaedic Institute, Bologna, Italy;6. National Research Council (CNR), Institute of Organic Synthesis and Photoreactivity (ISOF), Bologna, Italy;1. Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King''s College London, SE1 9NH, UK;2. School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK |
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| 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. |
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| Keywords: | Silver nanoparticles Autophagy Glioma Radiotherapy Radiation sensitization Cell signaling pathways |
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