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Research Article

三阴性乳腺癌顺铂耐药的转录组分析：对 PI3k/Akt 通路作用的新认识

卷 23, 期 6, 2023

发表于: 15 August, 2022

页: [559 - 568] 页: 10

弟呕挨: 10.2174/1566524022666220517102423

价格: $65

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摘要

背景：与其他乳腺癌类型相比，三阴性乳腺癌（TNBC）的侵袭性与预后不良相关。目前的指南推荐使用顺铂治疗 TNBC。然而，顺铂耐药性的发展是化疗失败的主要原因。 目的：在本研究中，我们旨在开发稳定的顺铂耐药 TNBC 细胞系，以研究顺铂耐药 TNBC 中涉及的关键通路和基因。 方法：将 MDA-MB-231 细胞暴露于不同浓度的顺铂。 33代后，细胞表现出耐药表型。然后，在顺铂耐药细胞系和亲代细胞系中进行 RNA 测序分析。通过定量 PCR（qPCR）验证 RNA 测序数据。 结果：耐药细胞的 IC50 增加到亲代细胞的10倍（p<0.001）。此外，顺铂耐药细胞显示出对其他药物的交叉耐药性，包括 5-氟尿嘧啶、紫杉醇和多柔比星。与亲代细胞相比，耐药细胞表现出药物积累减少。结果显示有 116 个差异表达基因 （DEG）（p<0.01）。基因本体分析表明，DEG 具有多种分子功能，包括结合和转运蛋白活性。功能注释显示DEGs富集于耐药相关通路，尤其是PI3K-Akt信号通路。在蛋白质-蛋白质相互作用网络中发现的最重要的基因是血红素加氧酶 1（HMOX1）和 TIMP 金属肽酶抑制剂 3（TIMP3）。 结论：我们已经确定了与 PI3KAkt 通路相关的若干通路和 DEG，这为顺铂耐药机制和 TNBC 中的潜在药物靶点提供了新的见解。

关键词: 顺铂，乳腺癌，耐药性，TNBC，PI3k / Akt，RNA-seq。

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