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

• Published in: Genes & cancer Vol. 10; no. 3-4; pp. 80 - 96
• Main Authors: Al-Jameel, Waseem, Gou, Xiaojun, Jin, Xi, Zhang, Jiacheng, Wei, Qiang, Ai, Jianzhong, Li, Hong, Al-Bayati, Asmaa, Platt-Higgins, Angela, Pettitt, Andrew, Rudland, Philip S, Ke, Youqiang
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 01-05-2019
• Subjects: Research Paper; tumorigenicity; FABP5; CRPC; dmrFABP5; PPARγ
• ISSN: 1947-6019; 1947-6027; 1947-6027
• DOI: 10.18632/genesandcancer.192

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
. 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
, 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.