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Basic Research

Targeted therapy with fatty acid synthase inhibitors in a human prostate carcinoma LNCaP/tk-luc-bearing animal model

Prostate Cancer and Prostatic Diseases volume 15, pages 260–264 (2012)Cite this article

Subjects

Abstract

Background:

Fatty acid synthase (FASN) is highly upregulated in human prostate carcinomas. Inhibition of FASN could arrest cell cycle and trigger apoptosis rapidly, implying the reliance of cancer cell survival on FASN. However, little is known about the effect of C75, a FASN inhibitor, and siFASN (that is, small interfering RNA targeted at FASN) on prostate cancer in living subjects.

Methods:

We used C75 and siFASN to mediate the endogenous fatty acid metabolism in LNCaP human prostate cancer cells stably expressing herpes simplex virus type 1 thymidine kinase (HSV1-tk) and luciferase (luc) reporter genes, and assessed the effect of FASN blockade with different schedules of administration on tumor growth using noninvasive molecular imaging.

Results:

FASN blockade exhibited the proliferative inhibition and induced G1-phase cell cycle arrest of LNCaP cells. For in vivo studies, the tumor growth inhibition by C75 (total 120 mg kg−1; 30 mg kg−1 once a week or 15 mg kg−1 twice a week for 4 weeks) and siFASN (1.4 mg kg−1 every alternate day up to 16 days) treatments were 80% and 70%, respectively, compared with that of the control.

Conclusion:

The results suggest that C75 may be superior to siFASN in anticancer effect on prostate cancer.

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Acknowledgements

This study was supported by the grant 97-2314-B-010-046-MY3 from the National Science Council, Taipei, Taiwan. We thank Molecular and Genetic Imaging Core (MAGIC) of the National Research Program for Genomic Medicine, Taiwan, for imaging services.

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Author notes

  1. H-W Chen and Y-F Chang: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Radiation Oncology, Mackay Memorial Hospital, Taipei, Taiwan

    H-W Chen

  2. Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan

    Y-F Chang, H-Y Chuang, W-T Tai & J-J Hwang

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  1. H-W Chen
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Corresponding author

Correspondence to J-J Hwang.

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Supplementary Information accompanies the paper on the Prostate Cancer and Prostatic Diseases website

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Chen, HW., Chang, YF., Chuang, HY. et al. Targeted therapy with fatty acid synthase inhibitors in a human prostate carcinoma LNCaP/tk-luc-bearing animal model. Prostate Cancer Prostatic Dis 15, 260–264 (2012). https://doi.org/10.1038/pcan.2012.15

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