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靶向前列腺癌中的核因子κB信号通路:一种有前景的治疗方法?

Targeting the NF-κB pathway in prostate cancer: a promising therapeutic approach?

作者信息

Verzella Daniela, Fischietti Mariafausta, Capece Daria, Vecchiotti Davide, Del Vecchio Filippo, Cicciarelli Germana, Mastroiaco Valentina, Tessitore Alessandra, Alesse Edoardo, Zazzeroni Francesca

机构信息

Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, Coppito II, 67100 L'Aquila, Italy.

出版信息

Curr Drug Targets. 2016;17(3):311-20. doi: 10.2174/1389450116666150907100715.

Abstract

Rel/NF-κB transcription factors are key regulators of genes implicated in inflammatory and immune activation, cell growth and protection from apoptosis. Constitutive activation of NF-κB has been observed in several types of cancers. Recently, it has been shown that inflammation and cancer are molecularly linked by means of NF-κB. During prostate cancer progression, NF-κB promotes cell survival, tumor invasion, metastasis and chemoresistance. NF-κB constitutive activation has been frequently demonstrated in primary prostate cancers and it correlates with loss of androgen receptor expression and castration-resistant phenotypes. Indeed, inhibition of NF-κB pathway may reduce the oncogenic effects mediated by chronic inflammatory response. Therefore, NF-κB represents a hopeful target for the treatment of prostate cancer due to its role in oncogenesis and chemoresistance. Here, the current knowledge about the roles of NF-κB signaling pathway in prostate tumorigenesis is discussed, taking into consideration the potentiality and effectiveness of NF-κB inhibitors as therapeutic agents for prostate cancer.

摘要

Rel/NF-κB转录因子是与炎症和免疫激活、细胞生长以及抗细胞凋亡相关基因的关键调节因子。在多种癌症类型中均观察到NF-κB的组成性激活。最近研究表明,炎症与癌症通过NF-κB在分子水平上存在关联。在前列腺癌进展过程中,NF-κB促进细胞存活、肿瘤侵袭、转移及化疗耐药。NF-κB的组成性激活在原发性前列腺癌中屡见不鲜,且与雄激素受体表达缺失及去势抵抗表型相关。事实上,抑制NF-κB信号通路可能会降低慢性炎症反应介导的致癌作用。因此,鉴于NF-κB在肿瘤发生和化疗耐药中的作用,它有望成为前列腺癌治疗的靶点。在此,我们讨论了关于NF-κB信号通路在前列腺肿瘤发生中作用的当前知识,并考虑了NF-κB抑制剂作为前列腺癌治疗药物的潜力和有效性。

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