无定形纳米SiO2诱导细胞恶性转化及其相关机制研究

项目名称： 无定形纳米SiO2诱导细胞恶性转化及其相关机制研究

项目编号： No.81202242

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 预防医学、地方病学、职业病学、放射医学

项目作者： 李艳博

作者单位： 首都医科大学

项目金额： 23万元

中文摘要： 结晶形二氧化硅（SiO2）被IARC划定为人类致癌物，而无定形SiO2为Group3，对动物和人类致癌的流行病学、实验室证据均有限、机制不清，深入探讨其与肿瘤关系很有必要。研究发现，无定形纳米SiO2可引发氧化应激，造成DNA损伤，增加肿瘤发生风险，且课题组研究发现纳米SiO2有致多核作用，而多核形成与细胞恶性转化及肿瘤发生密切相关。本项目研究纳米SiO2诱导人支气管上皮细胞16HBE恶性转化及相关作用机制，细胞多次纳米SiO2染毒，采用软琼脂集落形成、刀豆蛋白A凝集和裸鼠成瘤试验验证恶转发生，流式细胞术检测恶转前后ROS含量，Western blot检测ROS介导的MAPK/ERK和PI3K/Akt信号通路分子以及癌基因、抑癌基因表达，并应用ROS抑制剂NAC、H2O2及过表达/基因沉默ERK和Akt阐明上述信号通路在纳米SiO2诱导细胞恶转中的作用，为纳米SiO2安全性评价提供理论依据

中文关键词： 无定形纳米二氧化硅；氧化应激；恶性转化；遗传损伤；活性氧

英文摘要： Crystalline silica has already been designated as a human carcinogen by IARC. Due to the limited epidemiology and laboratory research evidence of carcinogenicity on animals and humans, and also its mechanism still unclear, the amorphous silica is classified as Group 3, and thus it is necessary to investigate its correlation with tumor. Researches showed that amorphous silica nanoparticle (nano-silica) could cause oxidative stress, induce DNA injury, and thus increase the risk of tumor occurrence. Furthermore, pevious study in our research group showed that amorphous nano-silica could induce the formation of multinucleation, which is also closely related to malignant transformation and carcinogenesis. Our project aims to investigate the malignant transformation of human bronchial epithelial cell, 16HBE induced by nano-silica and its related mechanisms. The 16HBE cells were exposed to nano-silica repeatedly, and the nano-silica-induced malignant transformation cell model was established eventually under the validation through soft agar colony formation, concanavealin A(ConA) agglutination and tumorigenecity in nude mice. The change of ROS content before and after the malignant transformation was determined by flow cytometry, and also the protein expressions of the signal molecules in the ROS-mediated MAPK/ERK and

英文关键词： amorphous silica nanoparticle；oxidative stress；malignant transformation；genetic injury；reactive oxygen species