南方医科大学学报2012，Vol.32Issue(8)：1093-1097,5.DOI:10.3969/j.issn.1673-4254.2012.08.05
干扰Nrf2可增强HirsutanolsA对肿瘤细胞增殖的抑制作用
Small interfering RNA-mediated Nrf2 gene knockdown enhances hirsutanols A-induced cytotoxity in cancer cells
摘要
Abstract
Objective To investigate the effect of Nrf2 gene knockdown on hirsutanols A-induced cytotoxity in cancer cells. Methods The changes in the cell viability following treatment with different concentrations of hirsutanols A was detected by Ml 1 assay, and the generation of reactive oxygen species (ROS) was assayed using flow cytometry. AnnexinV-FITC apoptosis kit was used to detect the cell apoptosis. Nrf2 protein expression in HepG2 and SW480 cells transfected with the siRNA targeting Nrf2 was analyzed with Western blotting. Results At the concentrations of 1.25, 2.5, 5, 10, 20 and 40 μmol/L, hirsutanols A obviously inhibited the cell proliferation of human liver cancer HepG2 and colon cancer SW480 cells in a concentration-dependent manner. The levels of hydrogen peroxide increased rapidly after hirsutanols A treatment in both HepG2 (30 μmol/L) and SW480 (15 μmol/L) cells. Hirsutanols A also induced apoptosis of the two cells. Pretreatment with 5 mmol/L NAC totally inhibited apoptosis and ROS accumulation in the two cells induced by hirsutanols A. Transfection of HepG2 and SW480 cells with the siRNA caused a significant reduction in Nrf2 protein expression, which resulted in an increased sensitivity of the cells to hirsutanols A. Conclusion Hirsutanols A can induce apoptosis in HepG2 and SW480 cells by promoting ROS production and up-regulating Nrf2 expression. Nrf2 knockdown by siRNA can increase the sensitivity of the cancer cells to hirsutanols A in vitro.关键词
Nrf2/HirsutanolsA/活性氧/凋亡Key words
Nrf2/ hirsutanols A/ reactive oxygen species/ apoptosis分类
医药卫生引用本文复制引用
马建国,李厚金,邓蓉,冯公侃,朱孝峰..干扰Nrf2可增强HirsutanolsA对肿瘤细胞增殖的抑制作用[J].南方医科大学学报,2012,32(8):1093-1097,5.基金项目
国家自然科学基金(81001446) （81001446）
