Hypoxia-induced autophagy as an additional mechanism in human osteosarcoma radioresistance
Osteosarcoma (OS) responds poorly to radiotherapy, but the mechanism is unclear. We found OS tumor tissues expressed high level of protein HIF-1α, a common biological marker indicative of hypoxia. It is known that hypoxic cells are generally radioresistant because of reduced production of irradiatio...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-06-01
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| Series: | Journal of Bone Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212137415300919 |
| _version_ | 1818422426836402176 |
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| author | Helin Feng Jin Wang Wei Chen Baoen Shan Yin Guo Jianfa Xu Ling Wang Peng Guo Yingze Zhang |
| author_facet | Helin Feng Jin Wang Wei Chen Baoen Shan Yin Guo Jianfa Xu Ling Wang Peng Guo Yingze Zhang |
| author_sort | Helin Feng |
| collection | DOAJ |
| description | Osteosarcoma (OS) responds poorly to radiotherapy, but the mechanism is unclear. We found OS tumor tissues expressed high level of protein HIF-1α, a common biological marker indicative of hypoxia. It is known that hypoxic cells are generally radioresistant because of reduced production of irradiation-induced DNA-damaging reactive oxygen species (ROS) in the anaerobic condition. Here we report another mechanism how hypoxia induces radioresistance. In MG-63 human osteosarcoma cells, hypoxic pretreatment increased the cellular survival in irradiation. These hypoxia-exposed cells displayed compartmental recruitment of GFP-tagged LC3 and expression of protein LC3-II, and restored the radiosensitivity upon autophagy inhibition. The following immunohistochemistry of OS tumor tissue sections revealed upregulated LC3 expression in a correlation with HIF-1α protein level, implying the possibly causative link between hypoxia and autophagy. Further studies in MG-63 cells demonstrated hypoxic pretreatment reduced cellular and mitochondrial ROS production during irradiation, while inhibition of autophagy re-elicited them. Taken together, our study suggests hypoxia can confer cells resistance to irradiation through activated autophagy to accelerate the clearance of cellular ROS products. This might exist in human osteosarcoma as an additional mechanism for radioresistance. |
| first_indexed | 2024-12-14T13:26:04Z |
| format | Article |
| id | doaj.art-e6e41e4de42b4e86bc701b4899158379 |
| institution | Directory Open Access Journal |
| issn | 2212-1374 |
| language | English |
| last_indexed | 2024-12-14T13:26:04Z |
| publishDate | 2016-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Bone Oncology |
| spelling | doaj.art-e6e41e4de42b4e86bc701b48991583792022-12-21T22:59:49ZengElsevierJournal of Bone Oncology2212-13742016-06-0152677310.1016/j.jbo.2016.03.001Hypoxia-induced autophagy as an additional mechanism in human osteosarcoma radioresistanceHelin Feng0Jin Wang1Wei Chen2Baoen Shan3Yin Guo4Jianfa Xu5Ling Wang6Peng Guo7Yingze Zhang8Department of Orthopedics, The Fourth Hospital of Hebei Medical University, 12 Health Road, Shijiazhuang, Hebei 050011, ChinaDepartment of Orthopedics, The Fourth Hospital of Hebei Medical University, 12 Health Road, Shijiazhuang, Hebei 050011, ChinaDepartment of Orthopedics, The Third Hospital of Hebei Medical University, 139 Ziqiang Road, Shijiazhuang, Hebei 050051, ChinaCancer Research Institute, The Fourth Hospital of Hebei Medical University, 12 Health Road, Shijiazhuang, Hebei 050011, ChinaDepartment of Radiation Oncology, The Fourth Hospital of Hebei Medical University, 12 Health Road, Shijiazhuang, Hebei 050011, ChinaDepartment of Orthopedics, The Fourth Hospital of Hebei Medical University, 12 Health Road, Shijiazhuang, Hebei 050011, ChinaCancer Research Institute, The Fourth Hospital of Hebei Medical University, 12 Health Road, Shijiazhuang, Hebei 050011, ChinaDepartment of Orthopedics, The Fourth Hospital of Hebei Medical University, 12 Health Road, Shijiazhuang, Hebei 050011, ChinaDepartment of Orthopedics, The Third Hospital of Hebei Medical University, 139 Ziqiang Road, Shijiazhuang, Hebei 050051, ChinaOsteosarcoma (OS) responds poorly to radiotherapy, but the mechanism is unclear. We found OS tumor tissues expressed high level of protein HIF-1α, a common biological marker indicative of hypoxia. It is known that hypoxic cells are generally radioresistant because of reduced production of irradiation-induced DNA-damaging reactive oxygen species (ROS) in the anaerobic condition. Here we report another mechanism how hypoxia induces radioresistance. In MG-63 human osteosarcoma cells, hypoxic pretreatment increased the cellular survival in irradiation. These hypoxia-exposed cells displayed compartmental recruitment of GFP-tagged LC3 and expression of protein LC3-II, and restored the radiosensitivity upon autophagy inhibition. The following immunohistochemistry of OS tumor tissue sections revealed upregulated LC3 expression in a correlation with HIF-1α protein level, implying the possibly causative link between hypoxia and autophagy. Further studies in MG-63 cells demonstrated hypoxic pretreatment reduced cellular and mitochondrial ROS production during irradiation, while inhibition of autophagy re-elicited them. Taken together, our study suggests hypoxia can confer cells resistance to irradiation through activated autophagy to accelerate the clearance of cellular ROS products. This might exist in human osteosarcoma as an additional mechanism for radioresistance.http://www.sciencedirect.com/science/article/pii/S2212137415300919OsteosarcomaRadioresistanceHypoxiaAutophagyHIF-1αLC3 |
| spellingShingle | Helin Feng Jin Wang Wei Chen Baoen Shan Yin Guo Jianfa Xu Ling Wang Peng Guo Yingze Zhang Hypoxia-induced autophagy as an additional mechanism in human osteosarcoma radioresistance Journal of Bone Oncology Osteosarcoma Radioresistance Hypoxia Autophagy HIF-1α LC3 |
| title | Hypoxia-induced autophagy as an additional mechanism in human osteosarcoma radioresistance |
| title_full | Hypoxia-induced autophagy as an additional mechanism in human osteosarcoma radioresistance |
| title_fullStr | Hypoxia-induced autophagy as an additional mechanism in human osteosarcoma radioresistance |
| title_full_unstemmed | Hypoxia-induced autophagy as an additional mechanism in human osteosarcoma radioresistance |
| title_short | Hypoxia-induced autophagy as an additional mechanism in human osteosarcoma radioresistance |
| title_sort | hypoxia induced autophagy as an additional mechanism in human osteosarcoma radioresistance |
| topic | Osteosarcoma Radioresistance Hypoxia Autophagy HIF-1α LC3 |
| url | http://www.sciencedirect.com/science/article/pii/S2212137415300919 |
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