Combination of sorafenib and enzalutamide as a potential new approach for the treatment of castration-resistant prostate cancer.
Combination of sorafenib and enzalutamide as a potential new approach for the treatment of castration-resistant prostate cancer.
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索拉非尼和恩杂鲁胺的组合作为治疗去势抵抗性前列腺癌的潜在新方法
DOI：
10.1016/j.canlet.2016.10.036
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发表时间：
2017-01
期刊：
影响因子：
9.7
通讯作者：
Yang Y
中科院分区：
文献类型：
--
作者：
Wu H;Zhang L;Gao X;Zhang X;Duan J;You L;Cheng Y;Bian J;Zhu Q;Yang Y
Enzalutamide是一种新型雄激素受体（AR）拮抗剂，可延长去势抵抗性前列腺癌（CRPC）患者的总生存期;然而，患者最终会进展为Enzalutamide耐药。我们在CRPC模型中研究了索拉非尼联合Enzalutamide的疗效，并探索了在体外和LNCaP异种移植物中提高Enzalutamide疗效的潜在策略。结果表明，Enzalutamide联合索拉非尼可有效降低前列腺癌细胞系LNCaP的细胞增殖并诱导细胞凋亡。在去势抵抗的LNCaP异种移植瘤中，Enzalutamide联合索拉非尼与单独使用相比，显著抑制了肿瘤生长。Western blot和免疫组化染色结果显示，联合用药后AR表达下调，细胞外信号调节激酶（ERK）信号通路受到抑制，提示联合用药对AR和ERK信号通路具有协同抑制作用。这些结果表明，索拉非尼治疗改善了Enzalutamide在CRPC模型中的疗效，表明临床CRPC患者的治疗策略很有前景。
Enzalutamide, a novel androgen receptor (AR) antagonist, prolongs overall survival of patients with castration-resistant prostate cancer (CRPC); however, patients eventually progress with enzalutamide resistance. We studied the efficacy of sorafenib combined with enzalutamide in a CRPC model and explored a potential strategy to improve enzalutamide efficacy in vitro and in LNCaP xenografts. The results indicated that enzalutamide combined with sorafenib potently decreased cell proliferation and induced apoptosis in the prostate cancer cell lineLNCaP. In castrate-resistant LNCaP xenografts, the combination of enzalutamide with sorafenib significantly suppressed tumor growth compared with eachsingle agent. Western blots and immunohistochemical staining assay showed that the expression of AR was down-regulated, and the extracellular signal-regulated kinase (ERK) signaling pathway was inhibited after combination treatment, suggesting a synergistic inhibitory effect on the AR and ERK pathways. These results demonstrated that sorafenib therapy improved the efficacy of enzalutamide in the CRPC model, indicating a promising therapeutic strategy for clinical CRPC patients.
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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