scholarly journals Overexpression of the opioid growth factor receptor potentiates growth inhibition in human pancreatic cancer cells

2007 ◽  
Author(s):  
Ian Zagon ◽  
Michael Verderame ◽  
Jody Hankins ◽  
Patricia McLaughlin
Keyword(s):  
Pancreatic Cancer ◽  
Growth Factor ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Growth Factor Receptor ◽  
Human Pancreatic Cancer ◽  
Opioid Growth Factor ◽  
Pancreatic Cancer Cells

scholarly journals Brusatol Enhances the Chemotherapy Efficacy of Gemcitabine in Pancreatic Cancer via the Nrf2 Signalling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Yukai Xiang ◽  
Wen Ye ◽  
Chaohao Huang ◽  
Dinglai Yu ◽  
Hao Chen ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Advanced Pancreatic Cancer ◽  
Signalling Pathway ◽  
Human Pancreatic Cancer ◽  
Control Treatment ◽  
Nrf2 Pathway ◽  
Pancreatic Cancer Cells ◽  
Nrf2 Activation

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 tumour growth compared with control treatment or treatment with either brusatol or gemcitabine alone. Immunohistochemical staining also showed that Nrf2 expression levels were reduced in brusatol-treated xenograft tumour tissues. In summary, our results suggest that brusatol is capable of enhancing the antitumour effects of gemcitabine in both pancreatic cancer cells and PANC-1 xenografts via suppressing the Nrf2 pathway.

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