BVAN08 enhances radiosensitivity via downregulation of DNA-PKcs towards hepatic tumor xenograft
BVAN08 enhances radiosensitivity via downregulation of DNA-PKcs towards hepatic tumor xenograft
复制标题
DOI：
10.1016/j.radmp.2020.08.002
复制
发表时间：
2020-08
期刊：
影响因子：
--
通讯作者：
Bo Zhang;Lantao Liu;Sai Hu;Zi-jian Yu;Dafei Xie;P. Zhou
中科院分区：
文献类型：
--
作者：
Bo Zhang;Lantao Liu;Sai Hu;Zi-jian Yu;Dafei Xie;P. Zhou
目的：研究新型香兰素类化合物BVAN08对肝癌细胞放射增敏的影响，为其作为潜在的放射增敏药物提供依据。方法：采用荧光素酶标记的肝癌细胞株Huh-7进行体内放射增敏实验。采用集落形成实验和流式细胞仪检测BVAN08体外培养的Huh-7细胞的凋亡率和放射敏感性。结果：BVAN08呈时间依赖性诱导Huh-7细胞凋亡和细胞周期停滞。此外，BVAN08联合放射治疗可提高HUH-7细胞对γ射线照射的敏感性，并显著抑制体内肿瘤生长。BVAN08治疗组、放疗组和联合治疗组的抑瘤率分别为58%、38%和85%。BVAN08治疗组肿瘤组织DNA-PKcs表达低于对照组(P<；0.01)。结论：BVAN08作为一种天然的食品添加剂衍生物，有望作为一种有效的抗癌药物，提高肿瘤细胞对放射治疗的敏感性。
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 BVAN08in vivo. Colony formation assays and flow cytometry were used to measure the apoptosis and radiosensitivity of Huh-7 cellsin vitroproduced by BVAN08. Histology and immunohistochemistry were used to evaluate the toxicity of BVAN08in 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 to γ-ray radiation and significantly inhibited tumor growthin 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.