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丙泊酚对他莫昔芬耐药乳腺癌细胞作用的功能分析:转录调控的见解

Functional analysis of the effects of propofol on tamoxifen‑resistant breast cancer cells: Insights into transcriptional regulation.

作者信息

Yin Runyang, Gao Jing, Liu Yang, Guo Chunyan

机构信息

Department of Anesthesiology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010050, P.R. China.

First Clinical Medical College, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010050, P.R. China.

出版信息

Oncol Lett. 2025 Feb 21;29(4):194. doi: 10.3892/ol.2025.14940. eCollection 2025 Apr.

Abstract

Although 70% of patients with estrogen receptor-positive breast cancer benefit from tamoxifen (TAM) therapy, the development of resistance to TAM leads to high rates of metastasis and a poor prognosis. Propofol, a commonly used anesthetic, can inhibit the occurrence and progression of breast cancer. In the present study, the effects of propofol on TAM-resistant (TR) breast cancer cells were evaluated. MCF7-TR cells were treated with or without propofol. Subsequently, cell cycle progression and the induction of apoptosis were detected by flow cytometry, whereas cell proliferation was assessed using Cell Counting Kit-8 and colony formation assays. Furthermore, the potential transcriptional regulatory effects of propofol on MCF7-TR cells were investigated using RNA sequencing. The results indicated that propofol significantly promoted cell cycle arrest, induced apoptosis, and inhibited proliferation and colony formation in MCF7-TR cells. Furthermore, transcriptome sequencing analysis revealed 1,065 differentially expressed genes between propofol-treated MCF7-TR and untreated MCF7-TR cells. Gene Ontology annotation enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and Gene Set Enrichment Analysis indicated that propofol affected the expression levels of genes located on the 'plasma membrane' and 'cell periphery', while mainly regulating signals involved in cancer biology, immune response and metabolic pathways. These results identified the potential effects of propofol on TR breast cancer cells and provided a theoretical basis for clinical treatment, particularly for individuals with TAM resistance.

摘要

尽管70%的雌激素受体阳性乳腺癌患者可从他莫昔芬(TAM)治疗中获益,但对TAM产生耐药性会导致高转移率和不良预后。丙泊酚是一种常用麻醉剂,可抑制乳腺癌的发生和进展。在本研究中,评估了丙泊酚对耐TAM(TR)乳腺癌细胞的影响。用或不用丙泊酚处理MCF7-TR细胞。随后,通过流式细胞术检测细胞周期进程和凋亡诱导情况,而使用细胞计数试剂盒-8和集落形成试验评估细胞增殖。此外,使用RNA测序研究丙泊酚对MCF7-TR细胞的潜在转录调控作用。结果表明,丙泊酚显著促进MCF7-TR细胞的细胞周期停滞,诱导凋亡,并抑制其增殖和集落形成。此外,转录组测序分析显示,丙泊酚处理的MCF7-TR细胞和未处理的MCF7-TR细胞之间有1065个差异表达基因。基因本体注释富集分析、京都基因与基因组百科全书通路富集分析和基因集富集分析表明,丙泊酚影响位于“质膜”和“细胞周边”的基因表达水平,同时主要调节与癌症生物学、免疫反应和代谢途径相关的信号。这些结果确定了丙泊酚对TR乳腺癌细胞的潜在作用,并为临床治疗,特别是对TAM耐药个体的治疗提供了理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b70/11878209/2119055a24b1/ol-29-04-14940-g00.jpg

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