BVAN08 enhances radiosensitivity via downregulation of DNA-PKcs towards hepatic tumor xenograft

查看全文 作　　者：Bo [1,2]Zhang;Lantao [3]Liu;Sai [4]Hu;Zi-Jian [5]Yu;Dafei [2]Xie;Pingkun [2]Zhou 机构地区：[1]College of Food Science and Engineering,Jinzhou Medical University,Jinzhou,Liaoning,121000,China;[2]Department of Radiation Biology,Beijing Key Laboratory for Radiobiology,Beijing Institute of Radiation Medicine,AMMS,Beijing,100850,China;[3]Beijing Institute for Occupational Disease Prevention and Treatment,Beijing,100093,China;[4]Institute for Environmental Medicine and Radiation Health,The College of Public Health,University of South China,Hengyang,Hunan,421001,China;[5]Department of Hepatobiliary Surgery,The First Affiliated Hospital,University of South China,Hengyang,Hunan,421001,China 出　　处：《Radiation Medicine and Protection》索引2020年第1卷第3期,共7页 基　　金：This study was supported by the National Natural Science Foundation of China(grant Nos.:31870847 and 11705283)and the foundation of Jinzhou Medical School。 摘　　要：Objective:To study the effects of the novel vanillin derivative BVAN08 on the radiosensitivity of hepatic cancer cells for the purpose of providing evidence for its potential use as a potential radiosensitive drug.Methods:Hepatic cancer Huh-7 cells labeled with luciferase were used to investigate the radiosensitivity induced by BVAN08 in vivo.Colony formation assays and flow cytometry were used to measure the apoptosis and radiosensitivity of Huh-7 cells in vitro produced by BVAN08.Histology and immunohistochemistry were used to evaluate the toxicity of BVAN08 in vivo.Results:BVAN08 induced apoptosis and cell cycle arrest of Huh-7 cells in a time-dependent manner.Moreover,BVAN08 combined with radiation increased the sensitivity of Huh-7 cells toγ-ray radiation and significantly inhibited tumor growth in vivo.The tumor inhibition rates of the BVAN08 treatment group,irradiation treatment group,and combined therapy group were 58%,38%,and 85%,respectively.The DNA-PKcs expression in tumor tissues of the BVAN08 treatment group was lower than that of the control group(P<0.01).BVAN08 inhibited the growth of Huh-7 cells in nude mice bearing tumors,without resulting in any noticeable side effects on bodyweight,livers,hearts,kidneys,or the number of peripheral white blood cells.Conclusions:As a natural food additive derivative,BVAN08 possesses the potential to be used as an effective anticancer drug to increase cell sensitivity to radiotherapy. 关 键 词：Vanillin derivative Cell cycle Apoptosis DNA-PKCS RADIOSENSITIVITY