Inactivated FABP5 suppresses malignant progression of prostate cancer cells by inhibiting the activation of nuclear fatty acid receptor PPARγ



Al-Jameel, W, Gou, X, Jin, X, Zhang, J, Wei, Q, Ai, J, Li, H, Al-Bayati, A, Platt-Higgins, A, Pettitt, A
et al (show 2 more authors) (2019) Inactivated FABP5 suppresses malignant progression of prostate cancer cells by inhibiting the activation of nuclear fatty acid receptor PPARγ. Genes and Cancer, 10 (3-4). 80 - 96.

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Abstract

© Al-Jameel et al. Previous study has suggested that the FABP5-PPARγ-signalling transduction pathway gradually replaces the androgen receptor activated pathway in promoting malignant progression of castration-resistant prostate cancer (CRPC) cells. To interfere with this newly discovered FABP5-related signalling pathway, we have produced a highly efficient recombinant FABP5 inhibitor, named dmrFABP5. Treatment with dmrFABP5 significantly supressed the proliferation, migration, invasion and colony formation of the highly malignant prostate cancer cells PC3-M in vitro. To test dmrFABP5’s suppressive effect in CRPC, the human PC3-M cells were implanted orthotopically into the prostate gland of immunosuppressed mice to produce tumours. These mice were then treated with dmrFABP5 and produced a highly significant reduction of 100% in metastatic rate and a highly significant reduction of 13-fold in the average size of primary tumours. Immunocytochemial staining showed that the staining intensity of dmrFABP5 treated tumours was reduced by 67%. When tested in vitro, dmrFABP5 suppressed the cancer cells by blocking fatty acid stimulation of PPARγ, and thereby prevented it activating down-stream cancer-promoting or inhibiting cancer-suppressing genes. Our results show that the FABP5 inhibitor dmrFABP5 is a novel molecule for treatment of experimental CRPC and its inhibitory effect is much greater than that produced by SB-FI-26 reported in our previous work.

Item Type: Article
Depositing User: Symplectic Admin
Date Deposited: 24 Jul 2019 09:05
Last Modified: 24 Jul 2019 09:05
DOI: 10.18632/oncoscience.192
URI: http://livrepository.liverpool.ac.uk/id/eprint/3050258
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