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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

将 AHSA1 鉴定为乳腺癌的潜在治疗靶点：生物信息学分析和体外研究

卷 22, 期 2, 2022

发表于: 14 February, 2022

页: [142 - 152] 页: 11

弟呕挨: 10.2174/1568009622666220114151058

价格: $65

摘要

背景：参苓白术散（SBP）是一种著名的中药（TCM）剂型，已广泛用于包括乳腺癌在内的癌症的辅助治疗。本研究旨在基于 SBP 的网络药理学确定乳腺癌治疗的潜在新靶点。 方法：通过分析药材与靶蛋白的关系，通过网络药理学分析确定多种药材在SBP中的潜在靶点。此外，通过比较乳腺癌组织与正常组织的数据，发现了两种乳腺癌表达谱中的上调基因。此后，通过生物信息学分析进一步分析了热休克蛋白90（HSP90）ATP酶活性1（AHSA1）激活剂在乳腺癌中的表达水平和预后，并构建了AHSA1结合蛋白的网络模块。此外，通过MTT、克隆形成试验和transwell试验验证了敲低AHSA1对乳腺癌细胞增殖、迁移和侵袭的影响。 结果：血管内皮生长因子 A (VEGFA)、细胞间粘附分子 1 (ICAM1)、趋化因子 (C-X-C 基序) 配体 8 (CXCL8)、AHSA1 和丝氨酸蛋白酶抑制剂家族 E 成员 1 (SERPINE1) 与 SBP 中的多种草药相关。 AHSA1 在乳腺癌组织中显着上调，并且与较差的总生存期和无疾病转移生存期呈正相关。此外，AHSA1的敲低显着抑制MCF-7和MDA-MB-231乳腺癌细胞的迁移和侵袭，但对增殖没有明显影响。此外，在与 AHSAl 结合的蛋白质中，由蛋白酶体、伴侣蛋白和热休克蛋白组成的网络紧密相连，这些蛋白质与多种癌症的预后不良有关。 结论：AHSA1与乳腺癌进展呈正相关，可能作为乳腺癌的新治疗靶点。

关键词: AHSA1，迁移，入侵，网络药理学，乳腺癌，申灵贝珠散。

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