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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

唑来膦酸抑制RhoA介导的前列腺癌细胞的运动性。

卷 19, 期 10, 2019

页: [807 - 816] 页: 10

弟呕挨: 10.2174/1568009619666190115142858

价格: $65

摘要

背景：双膦酸盐唑来膦酸（ZA）是一种有效的破骨细胞抑制剂，目前在临床上用于减少骨质疏松症和癌症引起的骨溶解。而且，ZA在几种肿瘤中发挥抗肿瘤作用。尽管有这些证据，但尚未完全了解ZA在前列腺癌（PCa）中的相关性。 目的：研究ZA给药对PC3细胞侵袭特性的影响，PC3细胞具有RhoA依赖的类动蛋白运动性。 方法：通过在3D胶原蛋白基质中进行细胞迁移，免疫荧光和Boyden分析或跨内皮迁移，评估ZA给药对PC3细胞体外侵袭特性的影响。进行肺保留和定植测定以评估体内ZA施用的功效。 结果：PC3细胞的特征在于依赖RhoA的变形虫运动。现在，我们报道了ZA治疗后对体外PC3细胞侵袭和RhoA活性的明显抑制。此外，为证实ZA在抑制PC3细胞的类阿米巴能动性中的特定作用，我们证明ZA仅由于部分用癌相关成纤维细胞的条件培养基处理或获得化学抗性而干扰显示间充质表型的PC3细胞。 此外，我们证明ZA损害了对内皮细胞的粘附和跨内皮细胞的迁移，这是表征阿米巴运动和PC3转移性传播的两个基本特性。体内实验证明了ZA抑制PC3细胞转移过程的能力，如肺部定植的减少所证明。 结论：这项研究表明，ZA抑制PC3细胞的Rho依赖的阿米巴运动，从而表明ZA是一种潜在的治疗方法，可阻止PC3细胞的转移性传播。

关键词: 前列腺癌，唑来膦酸，阿米巴运动，RhoA，转移，内皮。

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