The Nrf2 inhibitor brusatol is a potent antitumour agent in an orthotopic mouse model of colorectal cancer.

摘要: Nrf2 is a transcription factor that regulates cellular stress response and irinotecan-metabolising pathways. Its aberrant activity has been reported in number of cancers, although relatively few studies have explored role for colorectal cancer (CRC). This study assessed the expression patient CRC tissues effect modulation alone, or combination with irinotecan, human (HCT116) murine (CT26) cell lines vitro an orthotopic syngeneic mouse model utilising bioluminescent imaging. Using tissue microarray, was found to be overexpressed (p<0.01) primary metastatic relative normal colon, positive correlation between matched samples. In experiments revealed siRNA brusatol, which known inhibit Nrf2, decreased viability sensitised cells irinotecan toxicity. Furthermore, brusatol effectively abrogated tumour growth subcutaneously orthotopically-allografted mice, resulting average 8-fold reduction luminescence at end-point (p=0.02). Our results highlight as promising drug target treatment CRC.