Abstract

Elevated fatty acid synthase (FASN) has been reported in both androgen-dependent and -independent prostate cancers. Conventional treatment for prostate cancer is radiotherapy (RT); however, the following radiation-induced radioresistance often causes treatment failure. Upstream proteins of FASN such as Akt and NF-κB are found increased in the radioresistant prostate cancer cells. Nevertheless, whether inhibition of FASN could improve RT outcomes and reverse radiosensitivity of prostate cancer cells is still unknown. Here, we hypothesised that orlistat, a FASN inhibitor, could improve RT outcomes in prostate cancer. Orlistat treatment significantly reduced the S phase population in both androgen-dependent and -independent prostate cancer cells. Combination of orlistat and RT significantly decreased NF-κB activity and related downstream proteins in both prostate cancer cells. Combination effect of orlistat and RT was further investigated in both LNCaP and PC3 tumour-bearing mice. Combination treatment showed the best tumour inhibition compared to that of orlistat alone or RT alone. These results suggest that prostate cancer treated by conventional RT could be improved by orlistat via inhibition of FASN.

Details

Title
Fatty Acid Inhibition Sensitizes Androgen-Dependent and -Independent Prostate Cancer to Radiotherapy via FASN/NF-κB Pathway
Author
Hui-Yen, Chuang 1 ; Yen-Po, Lee 1 ; Wei-Chan, Lin 2 ; Yi-Hsien, Lin 3 ; Jeng-Jong Hwang 4 

 Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan 
 Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; Department of Radiology, Cathay General Hospital, Taipei, Taiwan; School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan 
 Division of Radiotherapy, Cheng Hsin General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan 
 Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan; Department of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan 
Pages
1-11
Publication year
2019
Publication date
Sep 2019
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2291326617
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.