Brusatol Enhances the Chemotherapy Efficacy of Gemcitabine in Pancreatic Cancer via the Nrf2 Signalling Pathway
Joint Authors
Zhou, Mengtao
Chen, Bi-Cheng
Zhang, Fan
Shi, Ke-Qing
Xiang, Yukai
Yu, Dinglai
Ye, Wen
Huang, Chaohao
Chen, Hao
Deng, Tuo
Lou, Bin
Zhang, Jie
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-04-18
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Xiang, Yukai& Ye, Wen& Huang, Chaohao& Yu, Dinglai& Chen, Hao& Deng, Tuo…[et al.]. 2018. Brusatol Enhances the Chemotherapy Efficacy of Gemcitabine in Pancreatic Cancer via the Nrf2 Signalling Pathway. Oxidative Medicine and Cellular Longevity،Vol. 2018, no. 2018, pp.1-10.
https://search.emarefa.net/detail/BIM-1211003
Modern Language Association (MLA)
Xiang, Yukai…[et al.]. Brusatol Enhances the Chemotherapy Efficacy of Gemcitabine in Pancreatic Cancer via the Nrf2 Signalling Pathway. Oxidative Medicine and Cellular Longevity No. 2018 (2018), pp.1-10.
https://search.emarefa.net/detail/BIM-1211003
American Medical Association (AMA)
Xiang, Yukai& Ye, Wen& Huang, Chaohao& Yu, Dinglai& Chen, Hao& Deng, Tuo…[et al.]. Brusatol Enhances the Chemotherapy Efficacy of Gemcitabine in Pancreatic Cancer via the Nrf2 Signalling Pathway. Oxidative Medicine and Cellular Longevity. 2018. Vol. 2018, no. 2018, pp.1-10.
https://search.emarefa.net/detail/BIM-1211003
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1211003