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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.
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Details
1 Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan
2 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
3 Division of Radiotherapy, Cheng Hsin General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan
4 Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan; Department of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan