Al-Jameel, Waseem, Gou, Xiaojun, Jin, Xi, Zhang, Jiacheng, Wei, Qiang, Ai, Jianzhong, Li, Hong, Al-Bayati, Asmaa, Platt-Higgins, Angela, Pettitt, Andrew 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 & cancer, 10 (3-4).
80 - 96.
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Abstract
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 |
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Depositing User: | Symplectic Admin |
Date Deposited: | 04 Jun 2019 07:57 |
Last Modified: | 19 Jan 2023 00:41 |
DOI: | 10.18632/genesandcancer.192 |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3043989 |
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- Inactivated FABP5 suppresses malignant progression of prostate cancer cells by inhibiting the activation of nuclear fatty acid receptor PPARγ. (deposited 04 Jun 2019 07:57) [Currently Displayed]