Brusatol Enhances the Chemotherapy Efficacy of Gemcitabine in Pancreatic Cancer via the Nrf2 Signalling Pathway
Abstract
Although gemcitabine is the standard chemotherapy treatment for advanced pancreatic cancer, its benefits are quite limited due to prevalent chemoresistance, and the mechanism underlying gemcitabine chemoresistance remains unclear. Currently, Nrf2 has been deemed as a significant contributor to gemcitabine chemoresistance in pancreatic cancer. Brusatol is a unique inhibitor of the Nrf2 pathway, and in previous studies, we determined that brusatol exhibits the effects of growth inhibition and proapoptosis in pancreatic cancer cells. Due to these data, we speculate that brusatol can reverse gemcitabine-induced Nrf2 activation and propose that it can enhance gemcitabine efficacy in treating pancreatic cancer. In this study, we first proved that brusatol can effectively inhibit the Nrf2 signalling pathway and increase ROS accumulation in pancreatic cancer cells. Next, we demonstrated that brusatol can abrogate gemcitabine-induced Nrf2 activation in pancreatic cancer cells. In addition, we discovered that brusatol potentiates gemcitabine-induced growth inhibition and apoptosis in human pancreatic cancer cells. In nude mice with PANC-1 xenografts, treatment with a combination of brusatol and gemcitabine considerably reduced in vivo tu...Continue Reading
References
Citations
Dual roles and therapeutic potential of Keap1-Nrf2 pathway in pancreatic cancer: a systematic review
Brusatol Inhibits Tumor Growth and Increases the Efficacy of Cabergoline against Pituitary Adenomas.
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