Comparative gene expression analysis of Nrf2 activators, CDDO-Im, CDDO-Me and dimethyl fumarate (DMF) in VC1 lung cancer cells. Mus musculus

Nrf2 is an important therapeutic target as activation of this pathway detoxifies harmful insults and reduces oxidative stress. However, the role of Nrf2 in cancer biology is controversial. Protection against oxidative stress and inflammation can confer a survival advantage to tumor cells, leading to a poor prognosis, and constitutive activation of Nrf2 has been detected in numerous tumors. In our study, we examined the role of two clinically relevant classes of Nrf2 activators, the synthetic triterpenoids (CDDO-Im and CDDO-Me) and dimethyl fumarate (DMF) in lung cancer. Using microarrays, we attempt to examine whether these Nrf2 activators have an effect on the same subset of Nrf2 genes. Overall design: VC1 lung cancer cells were treated with either DMSO, 0.05 uM of CDDO-Im, 0.1 uM of CDDO-Im or 15 uM of DMF for 6 hours before RNA was extracted by Qiagen RNeasy kit and analyzed using Illumina Micorarrays.

核因子红细胞2相关因子2（Nuclear factor erythroid 2-related factor 2, Nrf2）是一类重要的治疗靶点，因其通路激活可介导有害损伤的解毒过程并减轻氧化应激。然而，Nrf2在癌症生物学中的作用颇具争议。抗氧化应激与抗炎作用可赋予肿瘤细胞生存优势，进而导致不良预后，且已有多项研究在多种肿瘤中检测到Nrf2的组成型激活。
本研究针对两类临床相关的Nrf2激活剂展开探讨，即合成三萜类化合物（CDDO-Im与CDDO-Me）与富马酸二甲酯（dimethyl fumarate, DMF），并以肺癌为研究模型。我们借助基因芯片技术，旨在探究这些Nrf2激活剂是否会对同一组Nrf2靶基因产生相似调控效应。
整体实验设计：将VC1肺癌细胞分别用二甲基亚砜（dimethyl sulfoxide, DMSO）、0.05 μM CDDO-Im、0.1 μM CDDO-Im以及15 μM DMF处理6小时，随后采用Qiagen RNeasy试剂盒提取RNA，并通过Illumina基因芯片完成表达分析。