Comparable radiation sensitivity in p53 wild-type and p53 deficient tumor cells associated with different cell death modalities

doi:10.1038/s41420-021-00570-5

	Comparable radiation sensitivity in p53 wild-type and p53 deficient tumor cells associated with different cell death modalities
	Li, Ping 2,3,4,5; Liu, Xiongxiong 2,3,4,5; Zhao, Ting 2,3,4,5; Li, Feifei 6; Wang, Qiqi 6; Zhang, Pengcheng 2,3,4,5; Hirayama, Ryoichi 7; Chen, Weiqiang 2,3,4,5; Jin, Xiaodong 2,3,4,5; Zheng, Xiaogang 2,3,4,5
刊名	CELL DEATH DISCOVERY
	2021-07-20
卷号	7 期号:1 页码:8
DOI	10.1038/s41420-021-00570-5
通讯作者	Li, Qiang(liqiang@impcas.ac.cn)
英文摘要	Studies of radiation interaction with tumor cells often take apoptosis as the desired results. However, mitotic catastrophe and senescence are also promoted by clinically relevant doses of radiation. Furthermore, p53 is a well-known transcription factor that is closely associated with radiosensitivity and radiation-induced cell death. Therefore, we aimed to investigate the involvement of radiosensitivity, cell death modalities and p53 status in response to carbon-ion radiation (CIR) here. Isogenic human colorectal cancer cell lines HCT116 (p53(+/+) and p53(-/-)) were irradiated with high-LET carbon ions. Cell survival was determined by the standard colony-forming assay. 53BP1 foci were visualized to identify the repair kinetics of DNA double-strand breaks (DSBs). Cellular senescence was measured by SA-beta-Gal and Ki67 staining. Mitotic catastrophe was determined with DAPI staining. Comparable radiosensitivities of p53(+/+) and p53(-)(/-) HCT116 colorectal cells induced by CIR were demonstrated, as well as persistent 53BP1 foci indicated DNA repair deficiency in both cell lines. Different degree of premature senescence in isogenic HCT116 colorectal cancer cells suggested that CIR-induced premature senescence was more dependent on p21 but not p53. Sustained upregulation of p21 played multifunctional roles in senescence enhancement and apoptosis inhibition in p53(+/+) cells. p21 inhibition further increased radiosensitivity of p53(+/+) cells. Complex cell death modalities rather than single cell death were induced in both p53(+/+) and p53(-)(/-) cells after 5 Gy CIR. Mitotic catastrophe was predominant in p53(-)(/-) cells due to inefficient activation of Chk1 and Chk2 phosphorylation in combination with p53 null. Senescence was the major cell death mechanism in p53(+/+) cells via p21-dependent pathway. Taken together, p21-mediated premature senescence might be used by tumor cells to escape from CIR-induced cytotoxicity, at least for a time.
资助项目	National Key Research and Development Program of China[2017YFC0108500] ; National Key Research and Development Program of China[2017YFC0108503] ; National Natural Science Foundation of China[11705245] ; National Natural Science Foundation of China[11875299] ; National Natural Science Foundation of China[U1532264] ; Key Deployment Project of Chinese Academy of Sciences[KFZD-SW-222] ; Light of West China Program of Chinese Academy of Sciences[29Y86207]
WOS关键词	SENESCENCE ; CHECKPOINT ; APOPTOSIS ; CANCER ; MITOCHONDRIA ; MAINTENANCE ; IRRADIATION ; INHIBITION ; SURVIVAL ; ARREST
WOS研究方向	Cell Biology
语种	英语
出版者	SPRINGERNATURE
WOS记录号	WOS:000677525100001
资助机构	National Key Research and Development Program of China ; National Natural Science Foundation of China ; Key Deployment Project of Chinese Academy of Sciences ; Light of West China Program of Chinese Academy of Sciences
内容类型	期刊论文
源URL	[http://119.78.100.186/handle/113462/136756]
专题	中国科学院近代物理研究所
通讯作者	Li, Qiang
作者单位	1.Chinese Acad Med Sci, Peking Union Med Coll, Inst Med Biotechnol, Beijing, Peoples R China 2.Key Lab Basic Res Heavy Ion Radiat Applicat Med, Lanzhou, Gansu, Peoples R China 3.Chinese Acad Sci, Key Lab Heavy Ion Radiat Biol & Med, Lanzhou, Peoples R China 4.Chinese Acad Sci, Inst Modern Phys, Lanzhou, Peoples R China 5.Univ Chinese Acad Sci, Beijing, Peoples R China 6.Northwest Normal Univ, Coll Life Sci, Lanzhou, Peoples R China 7.Natl Inst Quantum & Radiol Sci & Technol QST, Inst Quantum Med Sci iQMS, Dept Charged Particle Therapy Res, Chiba, Japan
推荐引用方式 GB/T 7714	Li, Ping,Liu, Xiongxiong,Zhao, Ting,et al. Comparable radiation sensitivity in p53 wild-type and p53 deficient tumor cells associated with different cell death modalities[J]. CELL DEATH DISCOVERY,2021,7(1):8.
APA	Li, Ping.,Liu, Xiongxiong.,Zhao, Ting.,Li, Feifei.,Wang, Qiqi.,...&Li, Qiang.(2021).Comparable radiation sensitivity in p53 wild-type and p53 deficient tumor cells associated with different cell death modalities.CELL DEATH DISCOVERY,7(1),8.
MLA	Li, Ping,et al."Comparable radiation sensitivity in p53 wild-type and p53 deficient tumor cells associated with different cell death modalities".CELL DEATH DISCOVERY 7.1(2021):8.