机构：[1]Department of Molecular and Clinical Cancer Medicine, Liverpool University, Liverpool, United Kingdom[2]Sichuan Antibiotics Industrial Institute, Chengdu University, Chengdu, China[3]Institute of Urological Research, West China Hospital, Sichuan University, Chengdu, China四川大学华西医院[4]Department of Biochemistry, Liverpool University, Liverpool, United Kingdom[5]Department of Pathology, College of Veterinary Medicine, University of Mosul, Mosul, Iraq
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.
基金：
a scholarship from the High Committee for Educational Development (HCED) of the Iraqi Government. Some costs were met by a joint (XG and YK) International Cooperation grant from the Science and Technology Department, the Government of Sichuan Province, China (Grant Number: 2019YFH0054).
语种：
外文
PubmedID：
第一作者：
第一作者机构：[1]Department of Molecular and Clinical Cancer Medicine, Liverpool University, Liverpool, United Kingdom[5]Department of Pathology, College of Veterinary Medicine, University of Mosul, Mosul, Iraq
通讯作者：
推荐引用方式(GB/T 7714)：
Waseem Al-Jameel,Xiaojun Gou,Xi Jin,et al.Inactivated FABP5 suppresses malignant progression of prostate cancer cells by inhibiting the activation of nuclear fatty acid receptor PPARγ.[J].Genes & cancer.2019,10(3-4):80-96.doi:10.18632/genesandcancer.192.
APA：
Waseem Al-Jameel,Xiaojun Gou,Xi Jin,Jiacheng Zhang,Qiang Wei...&Youqiang Ke.(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)
MLA：
Waseem Al-Jameel,et al."Inactivated FABP5 suppresses malignant progression of prostate cancer cells by inhibiting the activation of nuclear fatty acid receptor PPARγ.".Genes & cancer 10..3-4(2019):80-96
