<br>FEN1 抑制作为一种潜在的乳腺癌新型靶向治疗以及 FEN1 的预后相关性,International Journal of Molecular Sciences

当前位置： X-MOL 学术 › Int. J. Mol. Sci. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

FEN1 抑制作为一种潜在的乳腺癌新型靶向治疗以及 FEN1 的预后相关性
International Journal of Molecular Sciences ( IF 4.9 ) Pub Date : 2024-02-09 , DOI: 10.3390/ijms25042110
Johanna Berfelde ₁ , Laura S Hildebrand _{1,

2} , Lukas Kuhlmann _{1,

2} , Rainer Fietkau _{1,

2} , Luitpold V Distel _{1,

2}

Affiliation

为了改善乳腺癌治疗并制定新的治疗耐药策略，人们不断研究治疗靶点。潜在的目标是 DNA 修复和复制以及基因组完整性的蛋白质，例如 Flap 核酸内切酶 1 (FEN1)。本研究调查了 FEN1 抑制剂 FEN1-IN-4 与电离辐射联合对乳腺癌细胞、乳腺细胞和健康细胞中的细胞死亡、克隆存活、细胞周期、衰老、倍增时间、DNA 双链断裂和微核的影响。皮肤成纤维细胞。此外，还研究了基线 FEN1 水平的变化及其对治疗预后的影响。这些细胞系在所研究的方面表现出特定的反应模式，并且具有异质基线 FEN1 水平。 FEN1-IN-4 具有细胞毒性、细胞抑制和放射增敏作用，通过细胞凋亡和坏死、G2M 共享、衰老、双链断裂和存活分数降低等增加细胞死亡来表达。然而，一些细胞受细胞毒性的影响较小，成纤维细胞的反应相当有限。在体内，FEN1 mRNA 高表达会使乳腺癌患者的预后恶化。由于乳腺癌组织中表达增加，FEN1 可能代表一种新的肿瘤和预后标志物，FEN1-IN-4 可能成为个性化医疗和乳腺癌靶向治疗的新有效药物。

"点击查看英文标题和摘要"

FEN1 Inhibition as a Potential Novel Targeted Therapy against Breast Cancer and the Prognostic Relevance of FEN1

To improve breast cancer treatment and to enable new strategies for therapeutic resistance, therapeutic targets are constantly being studied. Potential targets are proteins of DNA repair and replication and genomic integrity, such as Flap Endonuclease 1 (FEN1). This study investigated the effects of FEN1 inhibitor FEN1-IN-4 in combination with ionizing radiation on cell death, clonogenic survival, the cell cycle, senescence, doubling time, DNA double-strand breaks and micronuclei in breast cancer cells, breast cells and healthy skin fibroblasts. Furthermore, the variation in the baseline FEN1 level and its influence on treatment prognosis was investigated. The cell lines show specific response patterns in the aspects studied and have heterogeneous baseline FEN1 levels. FEN1-IN-4 has cytotoxic, cytostatic and radiosensitizing effects, expressed through increasing cell death by apoptosis and necrosis, G2M share, senescence, double-strand breaks and a reduced survival fraction. Nevertheless, some cells are less affected by the cytotoxicity and fibroblasts show a rather limited response. In vivo, high FEN1 mRNA expression worsens the prognosis of breast cancer patients. Due to the increased expression in breast cancer tissue, FEN1 could represent a new tumor and prognosis marker and FEN1-IN-4 may serve as a new potent agent in personalized medicine and targeted breast cancer therapy.

更新日期：2024-02-09

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文