Association of Cancer Stem Cell Radio-Resistance Under Ultra-High Dose Rate FLASH Irradiation With Lysosome-Mediated Autophagy.
Association of Cancer Stem Cell Radio-Resistance Under Ultra-High Dose Rate FLASH Irradiation With Lysosome-Mediated Autophagy.
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超高剂量率闪光照射下癌症干细胞的放射抗性与溶酶体介导的自噬的关联
DOI：
10.3389/fcell.2021.672693
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发表时间：
2021
影响因子：
5.5
通讯作者：
Yan X
中科院分区：
文献类型：
--
作者：
Yang G;Lu C;Mei Z;Sun X;Han J;Qian J;Liang Y;Pan Z;Kong D;Xu S;Liu Z;Gao Y;Qi G;Shou Y;Chen S;Cao Z;Zhao Y;Lin C;Zhao Y;Geng Y;Ma W;Yan X
癌症干细胞（CSC）被认为是放射抗性和放射治疗（RT）后复发的主要原因。最近，超高剂量率“FLASH-RT”与传统剂量率RT相比，因其在减少正常组织损伤的同时保持肿瘤反应而引起了人们的极大兴趣。然而，闪光照射（FLASH-IR）对CSC和正常癌细胞的杀伤作用和机制仍不清楚。目前正在研究CSC和正常癌细胞的辐射诱导死亡特征。通过激光加速纳秒粒子，以 6-9 Gy 的剂量用 FLASH-IR (∼109 Gy/s) 照射细胞。然后测定细胞凋亡、焦亡和坏死的比例。结果表明，FLASH-IR能够诱导不同比例的CSC和正常癌细胞发生凋亡、焦亡和坏死。在FLASH-IR下，CSC比正常癌细胞具有更强的抗辐射能力。进一步追踪溶酶体和自噬的实验表明，CSC 具有更高水平的溶酶体和自噬。综上所述，我们的结果表明，CSC的放射抗性可能与溶酶体介导的自噬的增加以及细胞凋亡、坏死和焦亡的减少有关。据我们有限的了解，这是第一篇揭示FLASH-IR对CSC和正常癌细胞的杀伤作用和死亡途径的报告。通过阐明FLASH-IR下CSC和正常癌细胞的死亡途径，可能有助于我们提高对CSC放射抗性的认识，从而有助于优化未来临床FLASH治疗方案。
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.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3.5
作者：
Li Chen;Tian Mei;Su Xu
通讯作者：
Su Xu
影响因子：
8.8
作者：
Dillon CP;Oberst A;Weinlich R;Janke LJ;Kang TB;Ben-Moshe T;Mak TW;Wallach D;Green DR
通讯作者：
Green DR
影响因子：
1.6
作者：
Doria, D.;Kakolee, K. F.;Borghesi, M.
通讯作者：
Borghesi, M.
鉴定非典型畸胎组织/色肽肿瘤中CD133阳性辐射细胞。
影响因子：
3.7
作者：
Chiou, Shih-Hwa;Kao, Chung-Lan;Chen, Yi-Wei;Chien, Chien-Shu;Hung, Shih-Chieh;Lo, Jeng-Fan;Chen, Yann-Jang;Ku, Hung-Hai;Hsu, Ming-Ta;Wong, Tai-Tong
通讯作者：
Wong, Tai-Tong