Oncotarget

Research Papers:

Inhibitor SBFI26 suppresses the malignant progression of castration-resistant PC3-M cells by competitively binding to oncogenic FABP5

Waseem Al-Jameel, Xiaojun Gou, Shiva S. Forootan, Majed Saad Al Fayi, Philip S. Rudland, Farzad S. Forootan, Jiacheng Zhang, Philip A. Cornford, Syed A. Hussain, Youqiang Ke _

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Oncotarget. 2017; 8:31041-31056. https://doi.org/10.18632/oncotarget.16055

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Abstract

Waseem Al-Jameel1, Xiaojun Gou2, Shiva S. Forootan1, Majed Saad Al Fayi1, Philip S. Rudland3, Farzad S. Forootan1, Jiacheng Zhang1, Philip A. Cornford1, Syed A. Hussain1, Youqiang Ke1

1Molecular Pathology Laboratory, Department of Molecular and Clinical Cancer Medicine, Liverpool University, Liverpool, L3 9TA, United Kingdom

2Sichuan Antibiotics Industrial Institute, Chengdu University, Chengdu 610081, China

3Department of Biochemistry, Liverpool University, Liverpool, L69 3GA, United Kingdom

Correspondence to:

Youqiang Ke, email: yqk@liverpool.ac.uk

Keywords: SBFI26, FABP5, CRPC, PPARγ, metastasis

Received: December 19, 2016     Accepted: February 27, 2017     Published: March 09, 2017

ABSTRACT

Castration resistant-prostate cancer is largely impervious to feather hormonal therapy and hence the outlook for patients is grim. Here we use an approach to attach the recently discovered Achilles heel. The experimental treatment established in this study is based on the recent discovery that it is the FABP5-PPARγ-VEGF signalling axis, rather than the androgen receptor pathway, played a dominant role in promoting the malignant progression of castration resistant prostate cancer cells. Treatments have been established in mice by suppressing the biological activity of FABP5 using a chemical inhibitor SBFI26. The inhibitor significantly suppressed the proliferation, migration, invasiveness and colony formation of PC3-M cells in vitro. It also produced a highly significant suppression of both the metastases and the primary tumours developed from cancer cells implanted orthotopically into the prostate glands of the mice. The inhibitor SBFI26 interferes with the FABP5-PPARγ- signalling pathway at the initial stage of the signal transduction by binding competitively to FABP5 to inhibit cellular fatty acid uptake. This avoids the fatty-acid stimulation of PPARγ and prevents it activating the down-stream regulated cancer-promoting genes. This entirely novel experimental approach to treating castration- resistant prostate cancer is completely different from current treatments that are based on androgen-blockade therapy.

Author Information

Waseem Al-Jameel

Xiaojun Gou

Shiva S. Forootan

Majed Saad Al Fayi

Philip S. Rudland

Farzad S. Forootan

Jiacheng Zhang

Philip A. Cornford

Syed A. Hussain

Youqiang Ke
Primary Contact  _


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