A549 cell proliferation inhibited by RNAi mediated silencing of the Nrf2 gene

Abstract

Non-small-cell lung cancer (NSCLC), the most common type of lung cancers, is resistant to initial chemotherapy intrinsically. The expressions of xenobiotic metabolism genes, antioxidants, and drug efflux proteins are increased in NSCLC. In addition, a redox-sensitive transcription factor named Nrf2 regulates the drug resistance via the expression of electrophile, oxidants detoxification enzymes and efflux mechanism. As was detected by real-time PCR, inhibiting Nrf2 expression through the transfection of shRNA plasmids in A549 cells significantly inhibits the expressions of glutathione pathway genes, antioxidants and multidrug resistance proteins. Using biochemical assays and free radical medical experiments in vitro, it was identified that the RNAi-mediated reduction of Nrf2 expression in lung cancer cells induces the generation of reactive oxygen species, decreases the level of reduced glutathione and results in an increase in the A549 cell proliferation inhibition rate. Thus, targeting Nrf2 activity in NSCLC could be a practical way to inhibit tumor growth and eliminate chemoresistance.