内皮素受体拮抗剂HJP 272及其在癌细胞迁移和侵袭中的作用

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2025-08-05 DOI:10.1016/j.tranon.2025.102492

Nabeela Baig , Rameswari Chilamakuri , Saurabh Agarwal , Aaron Muth , Sandra E. Reznik

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引用次数: 0

摘要

内皮素（ETs）是一个由21个氨基酸组成的多功能肽家族，具有ET-1、ET-2和ET-3三种异构体。ET-1是三种异构体中含量最多的，参与多种生物过程，如调节血管张力、体液稳态和神经嵴发育。然而，现在的重点是研究ET轴在不同类型肿瘤（包括卵巢癌、前列腺癌、乳腺癌、肺癌等）进展中的功能。HJP 272是一种新型的ETAR拮抗剂，虽然我们的研究小组以前研究过它对肺部炎症和早产的影响，但这项研究标志着它在癌症中的作用首次被探索。方法观察HJP 272在ET-1过表达细胞系MDA-MB-231 （TNBC）和A549 （NSCLC）中的体外活性。虽然HJP 272对癌细胞的生存能力没有影响，但我们观察到两种细胞系的迁移、侵袭和克隆生成能力都有显著的抑制作用。RNA-seq和western blot数据在体外证明了该化合物潜在的潜在分子机制。此外，在3D球体实验中，HJP 272对两种细胞系的肿瘤形成抑制能力进行了评估，发现MDA-MB-231细胞发生了显著变化，而A549细胞没有观察到显著变化。结论sour的工作提示HJP 272在肿瘤转移中的治疗潜力。两种细胞系之间的不同结果揭示了HJP 272在多种癌症类型中作用的潜在差异。

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HJP 272, an endothelin receptor antagonist, and its role in cancer cell migration and invasion

Introduction

Endothelins (ETs) are a family of versatile peptides composed of 21 amino acids with three isoforms: ET-1, ET-2, and ET-3. As the most abundant of the three isoforms, ET-1 is involved in various biological processes, such as regulation of vascular tone, humoral homeostasis, and neural crest development. However, focus is now being directed towards investigating the functions of the ET axis in the progression of different tumor types including ovarian, prostate, breast, lungs etc. HJP 272 is a novel ET_AR antagonist and while our group has previously researched its effects on lung inflammation and preterm birth, this study marks the first time its role in cancer has been explored.

Methods

We evaluated the in vitro activities of HJP 272 in the ET-1 and ET_AR overexpressing cell lines MDA-MB-231 (TNBC), and A549 (NSCLC). While HJP 272 had no effect on the viability of cancer cells, we observed a significant inhibition in the migration, invasion, and clonogenic capacities of both cell lines. RNA-seq and western blot data demonstrate the potential underlying molecular mechanisms of this compound in vitro. Furthermore, HJP 272 was evaluated in a 3D spheroid assay for its ability to inhibit tumor formation in both cell lines, revealing a significant change in MDA-MB-231 cells while no significant changes were observed in A549 cells.

Conclusions

Our work indicates a therapeutic potential for HJP 272 in cancer metastasis. The distinct outcomes between the two cell lines shed light on the potential differences of HJP 272′s effects across multiple cancer types.

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来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.