文献类型：期刊文献

中文题名：Effects of 12C6＋ heavy ion beam irradiation on the p53 signaling pathway in HepG2 liver cancer cells

英文题名：Effects of 12C6＋ heavy ion beam irradiation on the p53 signaling pathway in HepG2 liver cancer cells

作者：Kai Liu[1,2];Xinke Zhao[1,2];Jing Gu[2];Jianjun Wu[2];Hong Zhang[2];Yingdong Li[1,2,3]

第一作者：Kai Liu;刘凯

机构：[1]School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China;[2]Gansu University of Chinese Medicine, Lanzhou 730000, China;[3]Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Department of Heavy Ion Irradiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China

第一机构：School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China

年份：2017

卷号：49

期号：11

起止页码：989

中文期刊名：生物化学与生物物理学报：英文版

外文期刊名：Acta Biochimica et Biophysica Sinica

收录：CSTPCD;;Scopus;CSCD:【CSCD2017_2018】；PubMed;

基金：The work was supported by a grant from the Science Program of the Natural Science Foundation of China （No. 81160478）.

语种：中文

中文关键词：12C6+ 重离子横梁；HepG2；apoptosis；p53 发信号小径

外文关键词：12C6＋ heavy ion beam, HepG2, p53 signaling pathway, apoptosis

摘要：重离子横梁被认为是为放射疗法的理想的来源。细胞内部的 apoptosis 表明的 p53 肿瘤 suppressor 基因感觉 DNA 损坏和 transducts。以前的报告证明重离子横梁能触发细胞的 DNA 的损坏的复杂形式，导致房间周期拘捕和 HepG2 人的肝癌症房间的 apoptosis；然而，机制充分仍然保持不清楚。为了探索内在或外来的小径是否参与这，处理， HepG2 房间在 0 的剂量(控制)与12C6+ HIB 照耀被对待，有各种各样的方法的 1 ， 2 ， 4 ，和 6 Gy 采用了理解相关机制例如 apoptosis 的察觉，由流动 cytometry 的房间周期，和船边交货表示，由扫描共焦的显微镜学，并且屏蔽差别的电子显微镜学和激光的 apoptotic 形态学的分析表示了关于旁边表明小径的 p53 的基因这研究显示出在 6 Gy 的剂量的重离子横梁照耀导致的那 12C6+ 经由 synergistic 的人的 HepG2 房间的内长的 DNA 双海滨损坏， G2/M 房间周期拘捕，和 apoptosis 外来、内在的小径完成。差别在表明与 DNA 损坏修理， apoptosis，周期规定，转移，恶化和辐射抵抗有关的小径的 p53 表示了基因也被发现。因而，船边交货， TP53BP2， TP53AIP1，和 CASP9 的表情是在 12C6+ HIB 照耀处理以后的证实的 upregulated。在结论，这研究表明了 12C6+ 导致的抑制和 apoptosis 的机制 HepG2 癌症房间上的重离子横梁照耀被表明小径包括的 p53 的生物功能的开始调停外来、内在的 apoptosis 小径(吗？作者 2017。代表生物化学和房间生物学的研究所由牛津大学出版社出版了，为生物科学的上海研究所，中国科学院。版权所有。为权限，请发邮件：journals.permissions@oup.com。）
The heavy ion beam is considered to be the ideal source for radiotherapy. The p53 tumor suppressor gene senses DNA damage and transducts intracellular apoptosis signals. Previous reports showed that the heavy ion beam can trigger complex forms of damage to cellular DNA, leading to cell cycle arrest and apoptosis of HepG2 human liver cancer cells; however, the mechanisms remains unclear fully. In order to explore whether the intrinsic or extrinsic pathway participates this process, HepG2 cells were treated with 1206＋ HIB irradiation at doses of 0 （control）, 1, 2, 4, and 6Gy with various methods employed to understand relevant mechanisms, such as detection of apoptosis, cell cycle, and Fas expression by flow cytometry, analysis of apoptotic morphology by electron microscopy and laser scanning confocal microscopy, and screening differentially expressed genes relating to p53 signaling pathway by PCR-array assay following with any genes confirmed by western blot analysis. This study showed that 1206＋ heavy ion beam irradiation at a dose of 6 Gy leads to endogenous DNA double-strand damage, G2/M cell cycle arrest, and apop- tosis of human HepG2 cells via synergistic effect of the extrinsic and intrinsic pathways. Differentially expressed genes in the p53 signaling pathway related to DNA damage repair, apop- tosis, cycle regulation, metastasis, deterioration and radioresistance were also discovered. Consequently, the expressions of Fas, TP53BP2, TP53AIP1, and CASP9 were confirmed upregu- lated after 1206＋ HIB irradiation treatment. In conclusion, this study demonstrated the mechanisms of inhibition and apoptosis induced by 1206＋ heavy ion beam irradiation on HepG2 cancer cells is mediated by initiation of the biological function of p53 signaling pathway including extrinsic and intrinsic apoptosis pathway.