Association of Cancer Stem Cell Radio-Resistance Under Ultra-High Dose Rate FLASH Irradiation With Lysosome-Mediated Autophagy
Cancer stem cell (CSC) is thought to be the major cause of radio-resistance and relapse post radiotherapy (RT). Recently ultra-high dose rate “FLASH-RT” evokes great interest for its decreasing normal tissue damages while maintaining tumor responses compared with conventional dose rate RT. However,...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.672693/full |
| id |
doaj-2717a46833c94ea89b91edb431e86d1b |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Gen Yang Chunyang Lu Zhusong Mei Xiaoyi Sun Jintao Han Jing Qian Yulan Liang Zhuo Pan Defeng Kong Shirui Xu Zhipeng Liu Ying Gao Guijun Qi Yinren Shou Shiyou Chen Zhengxuan Cao Ye Zhao Chen Lin Yanying Zhao Yixing Geng Wenjun Ma Xueqing Yan Xueqing Yan |
| spellingShingle |
Gen Yang Chunyang Lu Zhusong Mei Xiaoyi Sun Jintao Han Jing Qian Yulan Liang Zhuo Pan Defeng Kong Shirui Xu Zhipeng Liu Ying Gao Guijun Qi Yinren Shou Shiyou Chen Zhengxuan Cao Ye Zhao Chen Lin Yanying Zhao Yixing Geng Wenjun Ma Xueqing Yan Xueqing Yan Association of Cancer Stem Cell Radio-Resistance Under Ultra-High Dose Rate FLASH Irradiation With Lysosome-Mediated Autophagy Frontiers in Cell and Developmental Biology ultra-high dose rate irradiation FLASH DNA damage lysosome cancer stem cell autophagy |
| author_facet |
Gen Yang Chunyang Lu Zhusong Mei Xiaoyi Sun Jintao Han Jing Qian Yulan Liang Zhuo Pan Defeng Kong Shirui Xu Zhipeng Liu Ying Gao Guijun Qi Yinren Shou Shiyou Chen Zhengxuan Cao Ye Zhao Chen Lin Yanying Zhao Yixing Geng Wenjun Ma Xueqing Yan Xueqing Yan |
| author_sort |
Gen Yang |
| title |
Association of Cancer Stem Cell Radio-Resistance Under Ultra-High Dose Rate FLASH Irradiation With Lysosome-Mediated Autophagy |
| title_short |
Association of Cancer Stem Cell Radio-Resistance Under Ultra-High Dose Rate FLASH Irradiation With Lysosome-Mediated Autophagy |
| title_full |
Association of Cancer Stem Cell Radio-Resistance Under Ultra-High Dose Rate FLASH Irradiation With Lysosome-Mediated Autophagy |
| title_fullStr |
Association of Cancer Stem Cell Radio-Resistance Under Ultra-High Dose Rate FLASH Irradiation With Lysosome-Mediated Autophagy |
| title_full_unstemmed |
Association of Cancer Stem Cell Radio-Resistance Under Ultra-High Dose Rate FLASH Irradiation With Lysosome-Mediated Autophagy |
| title_sort |
association of cancer stem cell radio-resistance under ultra-high dose rate flash irradiation with lysosome-mediated autophagy |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Cell and Developmental Biology |
| issn |
2296-634X |
| publishDate |
2021-04-01 |
| description |
Cancer stem cell (CSC) is thought to be the major cause of radio-resistance and relapse post radiotherapy (RT). Recently ultra-high dose rate “FLASH-RT” evokes great interest for its decreasing normal tissue damages while maintaining tumor responses compared with conventional dose rate RT. However, the killing effect and mechanism of FLASH irradiation (FLASH-IR) on CSC and normal cancer cell are still unclear. Presently the radiation induced death profile of CSC and normal cancer cell were studied. Cells were irradiated with FLASH-IR (∼109 Gy/s) at the dose of 6–9 Gy via laser-accelerated nanosecond particles. Then the ratio of apoptosis, pyroptosis and necrosis were determined. The results showed that FLASH-IR can induce apoptosis, pyroptosis and necrosis in both CSC and normal cancer cell with different ratios. And CSC was more resistant to radiation than normal cancer cell under FLASH-IR. Further experiments tracing lysosome and autophagy showed that CSCs had higher levels of lysosome and autophagy. Taken together, our results suggested that the radio-resistance of CSC may associate with the increase of lysosome-mediated autophagy, and the decrease of apoptosis, necrosis and pyroptosis. To our limited knowledge, this is the first report shedding light on the killing effects and death pathways of CSC and normal cancer cell under FLASH-IR. By clarifying the death pathways of CSC and normal cancer cell under FLASH-IR, it may help us improve the understanding of the radio-resistance of CSC and thus help to optimize the future clinical FLASH treatment plan. |
| topic |
ultra-high dose rate irradiation FLASH DNA damage lysosome cancer stem cell autophagy |
| url |
https://www.frontiersin.org/articles/10.3389/fcell.2021.672693/full |
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1721501584655908864 |
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doaj-2717a46833c94ea89b91edb431e86d1b2021-04-29T05:22:35ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-04-01910.3389/fcell.2021.672693672693Association of Cancer Stem Cell Radio-Resistance Under Ultra-High Dose Rate FLASH Irradiation With Lysosome-Mediated AutophagyGen Yang0Chunyang Lu1Zhusong Mei2Xiaoyi Sun3Jintao Han4Jing Qian5Yulan Liang6Zhuo Pan7Defeng Kong8Shirui Xu9Zhipeng Liu10Ying Gao11Guijun Qi12Yinren Shou13Shiyou Chen14Zhengxuan Cao15Ye Zhao16Chen Lin17Yanying Zhao18Yixing Geng19Wenjun Ma20Xueqing Yan21Xueqing Yan22State Key Laboratory of Nuclear Physics and Technology, School of Physics, CAPT, Peking University, Beijing, ChinaState Key Laboratory of Nuclear Physics and Technology, School of Physics, CAPT, Peking University, Beijing, ChinaState Key Laboratory of Nuclear Physics and Technology, School of Physics, CAPT, Peking University, Beijing, ChinaState Key Laboratory of Nuclear Physics and Technology, School of Physics, CAPT, Peking University, Beijing, ChinaState Key Laboratory of Nuclear Physics and Technology, School of Physics, CAPT, Peking University, Beijing, ChinaTeaching and Research Section of Nuclear Medicine, School of Basic Medical Sciences, Anhui Medical University, Hefei, ChinaState Key Laboratory of Nuclear Physics and Technology, School of Physics, CAPT, Peking University, Beijing, ChinaState Key Laboratory of Nuclear Physics and Technology, School of Physics, CAPT, Peking University, Beijing, ChinaState Key Laboratory of Nuclear Physics and Technology, School of Physics, CAPT, Peking University, Beijing, ChinaState Key Laboratory of Nuclear Physics and Technology, School of Physics, CAPT, Peking University, Beijing, ChinaState Key Laboratory of Nuclear Physics and Technology, School of Physics, CAPT, Peking University, Beijing, ChinaState Key Laboratory of Nuclear Physics and Technology, School of Physics, CAPT, Peking University, Beijing, ChinaState Key Laboratory of Nuclear Physics and Technology, School of Physics, CAPT, Peking University, Beijing, ChinaState Key Laboratory of Nuclear Physics and Technology, School of Physics, CAPT, Peking University, Beijing, ChinaState Key Laboratory of Nuclear Physics and Technology, School of Physics, CAPT, Peking University, Beijing, ChinaState Key Laboratory of Nuclear Physics and Technology, School of Physics, CAPT, Peking University, Beijing, ChinaTeaching and Research Section of Nuclear Medicine, School of Basic Medical Sciences, Anhui Medical University, Hefei, ChinaState Key Laboratory of Nuclear Physics and Technology, School of Physics, CAPT, Peking University, Beijing, ChinaState Key Laboratory of Nuclear Physics and Technology, School of Physics, CAPT, Peking University, Beijing, ChinaState Key Laboratory of Nuclear Physics and Technology, School of Physics, CAPT, Peking University, Beijing, ChinaState Key Laboratory of Nuclear Physics and Technology, School of Physics, CAPT, Peking University, Beijing, ChinaState Key Laboratory of Nuclear Physics and Technology, School of Physics, CAPT, Peking University, Beijing, ChinaCollaborative Innovation Center of Extreme Optics, Shanxi University, Taiyuan, ChinaCancer stem cell (CSC) is thought to be the major cause of radio-resistance and relapse post radiotherapy (RT). Recently ultra-high dose rate “FLASH-RT” evokes great interest for its decreasing normal tissue damages while maintaining tumor responses compared with conventional dose rate RT. However, the killing effect and mechanism of FLASH irradiation (FLASH-IR) on CSC and normal cancer cell are still unclear. Presently the radiation induced death profile of CSC and normal cancer cell were studied. Cells were irradiated with FLASH-IR (∼109 Gy/s) at the dose of 6–9 Gy via laser-accelerated nanosecond particles. Then the ratio of apoptosis, pyroptosis and necrosis were determined. The results showed that FLASH-IR can induce apoptosis, pyroptosis and necrosis in both CSC and normal cancer cell with different ratios. And CSC was more resistant to radiation than normal cancer cell under FLASH-IR. Further experiments tracing lysosome and autophagy showed that CSCs had higher levels of lysosome and autophagy. Taken together, our results suggested that the radio-resistance of CSC may associate with the increase of lysosome-mediated autophagy, and the decrease of apoptosis, necrosis and pyroptosis. To our limited knowledge, this is the first report shedding light on the killing effects and death pathways of CSC and normal cancer cell under FLASH-IR. By clarifying the death pathways of CSC and normal cancer cell under FLASH-IR, it may help us improve the understanding of the radio-resistance of CSC and thus help to optimize the future clinical FLASH treatment plan.https://www.frontiersin.org/articles/10.3389/fcell.2021.672693/fullultra-high dose rate irradiationFLASHDNA damagelysosomecancer stem cellautophagy |