失活的FABP5通过抑制核脂肪酸受体PPARγ的激活来抑制前列腺癌细胞的恶性进展。

Q2 Biochemistry, Genetics and Molecular Biology
Waseem Al-Jameel, Xiaojun Gou, Xi Jin, Jiacheng Zhang, Qiang Wei, Jianzhong Ai, Hong Li, Asmaa Al-Bayati, Angela Platt-Higgins, Andrew Pettitt, Philip S Rudland, Youqiang Ke
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引用次数: 20

摘要

既往研究表明,fabp5 - ppar γ信号转导通路逐渐取代雄激素受体激活通路,促进去势抵抗性前列腺癌(CRPC)细胞的恶性进展。为了干扰这个新发现的FABP5相关信号通路,我们生产了一种高效的重组FABP5抑制剂,命名为dmrFABP5。dmrFABP5可显著抑制体外高度恶性前列腺癌细胞PC3-M的增殖、迁移、侵袭和集落形成。为了检测dmrFABP5对CRPC的抑制作用,我们将人PC3-M细胞原位植入免疫抑制小鼠的前列腺,使其产生肿瘤。然后用dmrFABP5治疗这些小鼠,转移率显著降低100%,原发肿瘤的平均大小显著降低13倍。免疫细胞化学染色显示dmrFABP5处理的肿瘤染色强度降低67%。在体外实验中,dmrFABP5通过阻断脂肪酸对PPARγ的刺激来抑制癌细胞,从而阻止其激活下游促癌或抑制抑癌基因。我们的研究结果表明,FABP5抑制剂dmrFABP5是一种治疗实验性CRPC的新分子,其抑制作用远远大于我们之前报道的SB-FI-26。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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

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

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

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.

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来源期刊
Genes and Cancer
Genes and Cancer Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
3.90
自引率
0.00%
发文量
6
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