沉默 PCMT1 可通过 PI3K/Akt/STMN1 通路提高乳腺癌细胞对紫杉醇的敏感性。

IF 3.2 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Ke Zhang, Jin-You Li, Kai Li
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引用次数: 0

摘要

本研究旨在探讨沉默L-异天冬氨酸(D-天冬氨酸)蛋白O-甲基转移酶(PCMT1)的表达能否提高乳腺癌细胞对紫杉醇的敏感性及其可能的机制。肿瘤组织和邻近组织学正常组织均取自本院收治的乳腺癌患者。购买人正常乳腺上皮细胞 MCF10A、人乳腺癌细胞 MCF-7 和紫杉醇耐药乳腺癌细胞 MCF-7/PR。MCF-7/PR 细胞被进一步分为阴性对照(NC)组、si-PCMT1 组(转染 si-PCMT1)、740Y-P 组(用 740Y-P 处理,740Y-P 是磷脂酰肌醇 3- 激酶(PI3K)/ v-Akt 默沙东胸腺瘤病毒癌基因(AKT)信号通路的激活剂)和 si-PCMT1 + 740Y-P 组(转染 si-PCMT1,然后用 740Y-P 处理)。组织和细胞中 PCMT1 的表达水平通过实时定量聚合酶链反应(qRT-PCR)检测。Western 印迹分析用于检测组织和细胞中 PCMT1 的蛋白表达水平,以及细胞中 p-PI3K、PI3K、p-Akt、Akt 和 Stathmin1 (STMN1) 的蛋白水平。3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) 和菌落形成试验用于测定细胞活力,划痕试验用于评估细胞的迁移能力,Transwell 试验用于评估细胞的侵袭能力。结果表明,PCMT1 在乳腺癌组织和 MCF-7/PR 细胞中明显上调。抑制 PCMT1 的表达可明显抑制 MCF-7/PR 细胞的增殖、迁移和侵袭,并减轻癌细胞对紫杉醇的耐药性。此外,沉默 PCMT1 还能抑制 MCF-7/PR 细胞中 PI3K/Akt/STMN1 通路的激活,而激活 PI3K/Akt/STMN1 通路则能明显逆转沉默 PCMT1 对 MCF-7/PR 细胞的影响。PCMT1 在乳腺癌组织和 MCF-7/PR 细胞中高表达,沉默 PCMT1 不仅能抑制乳腺癌的发展,还能提高紫杉醇的敏感性。其作用机制可能是通过抑制 PI3K/Akt/STMN1 信号转导实现的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Silencing PCMT1 enhances the sensitivity of breast cancer cells to paclitaxel through the PI3K/Akt/STMN1 pathway

Silencing PCMT1 enhances the sensitivity of breast cancer cells to paclitaxel through the PI3K/Akt/STMN1 pathway

This study aimed to investigate whether silencing Protein L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1) expression can enhance the sensitivity of breast cancer cells to paclitaxel and its possible mechanism. Tumor tissues and adjacent histologically normal tissues were collected from patients with breast cancer admitted to our hospital. Human normal breast epithelial cells MCF10A, human breast cancer cells MCF-7, and paclitaxel-resistant breast cancer cells MCF-7/PR were purchased. MCF-7/PR cells were further grouped into negative control (NC) group, si-PCMT1 group (transfected with si-PCMT1), 740Y-P group (treated with 740Y-P, an activator of phosphatidylinositol 3-kinase (PI3K)/ v-Akt Murine Thymoma Viral Oncogene (AKT) signaling pathway), and si-PCMT1 + 740Y-P group (transfected with si-PCMT1 and then treated with 740Y-P). The expression level of PCMT1 in tissues and cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot analysis was used to detect the protein expression level of PCMT1 in tissues and cells as well as the protein level of p-PI3K, PI3K, p-Akt, Akt, and Stathmin1 (STMN1) in cells. 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and colony formation assays were used to determine cell viability, scratch assay was used to assess the migration ability of cells, and Transwell assay was used to assess the invasion ability of cells. The expression of PCMT1 was remarkably up-regulated in breast cancer tissues and MCF-7/PR cells. Silencing PCMT1 expression significantly inhibited the proliferation, migration, and invasion of MCF-7/PR cells, and alleviated the resistance of cancer cells to paclitaxel. Additionally, silencing PCMT1 expression also inhibited the activation of PI3K/Akt/STMN1 pathway in MCF-7/PR cells, while activating PI3K/Akt/STMN1 pathway significantly reversed the effect of silencing PCMT1 expression on MCF-7/PR cells. PCMT1 is highly expressed in breast cancer tissues and MCF-7/PR cells, and silencing PCMT1 expression can not only inhibit the development of breast cancer but also enhance paclitaxel sensitivity. Its mechanism of action may be achieved by inhibiting PI3K/Akt/STMN1 signaling.

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来源期刊
Chemical Biology & Drug Design
Chemical Biology & Drug Design 医学-生化与分子生物学
CiteScore
5.10
自引率
3.30%
发文量
164
审稿时长
4.4 months
期刊介绍: Chemical Biology & Drug Design is a peer-reviewed scientific journal that is dedicated to the advancement of innovative science, technology and medicine with a focus on the multidisciplinary fields of chemical biology and drug design. It is the aim of Chemical Biology & Drug Design to capture significant research and drug discovery that highlights new concepts, insight and new findings within the scope of chemical biology and drug design.
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