文献类型：期刊文献

英文题名：Effects of C-12(6+) heavy ion beam irradiation on the p53 signaling pathway in HepG2 liver cancer cells

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

第一作者：Liu, Kai;刘凯

通信作者：Li, YD[1];Li, YD[2];Li, YD[3]

机构：[1]Lanzhou Univ, Sch Basic Med Sci, Lanzhou 730000, Gansu, Peoples R China;[2]Gansu Univ Chinese Med, Lanzhou 730000, Gansu, Peoples R China;[3]Chinese Acad Sci, Key Lab Heavy Ion Radiat Biol & Med, Dept Heavy Ion Irradiat Med, Inst Modern Phys, Lanzhou 730000, Gansu, Peoples R China

第一机构：Lanzhou Univ, Sch Basic Med Sci, Lanzhou 730000, Gansu, Peoples R China

通信机构：[1]corresponding author), Lanzhou Univ, Sch Basic Med Sci, Lanzhou 730000, Gansu, Peoples R China;[2]corresponding author), Gansu Univ Chinese Med, Lanzhou 730000, Gansu, Peoples R China;[3]corresponding author), Chinese Acad Sci, Key Lab Heavy Ion Radiat Biol & Med, Dept Heavy Ion Irradiat Med, Inst Modern Phys, Lanzhou 730000, Gansu, Peoples R China.|[10735]甘肃中医药大学;

年份：2017

卷号：49

期号：11

起止页码：989

外文期刊名：ACTA BIOCHIMICA ET BIOPHYSICA SINICA

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000418269100004)】；

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

语种：英文

外文关键词：C-12(6+) heavy ion beam; HepG2; p53 signaling pathway; apoptosis

摘要：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 C-12(6+) HIB irradiation at doses of 0 (control), 1, 2, 4, and 6 Gy 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 C-12(6+) heavy ion beam irradiation at a dose of 6 Gy leads to endogenous DNA double-strand damage, G2/M cell cycle arrest, and apoptosis 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, apoptosis, cycle regulation, metastasis, deterioration and radioresistance were also discovered. Consequently, the expressions of Fas, TP53BP2, TP53AIP1, and CASP9 were confirmed upregulated after C-12(6+) HIB irradiation treatment. In conclusion, this study demonstrated the mechanisms of inhibition and apoptosis induced by C-12(6+) 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.