Study on the anticancer mechanism of hydroxygenkwanin in esophageal cancer via the ESRRA signaling pathway

IF 11 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics Pub Date : 2025-11-01 Epub Date: 2025-09-26 DOI:10.1016/j.cancergen.2025.09.011

Yuan Wang , Xin Wan , Yutian Zhang , Jia Qi , Chao Li , Xiaonan Cui

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引用次数: 0

Abstract

Objective

To explore the role of ESRRA in esophageal squamous cell carcinoma (ESCC) progression and evaluate the antitumor effects of hydroxygenkwanin (HGK), focusing on its interaction with ESRRA and the underlying molecular mechanisms.

Methods

Cell viability, apoptosis, invasion, and proliferation were assessed in EC109 and TE-1 cells treated with HGK using CCK-8, Hoechst staining, Transwell, and colony formation assays. ESRRA expression was analyzed via qPCR and Western blot. An ESCC mouse model was established, with treatment groups receiving HGK. Serum IL-10 and IL-12 levels were measured by ELISA; tumor growth and toxicity were evaluated by histology. EMT marker expression was analyzed by IHC and RT-qPCR. TCGA database analysis explored ESRRA-related pathways and its link to the tumor microenvironment and patient survival.

Results

HGK inhibited EC109 and TE-1 cell proliferation and migration, especially in EC109 cells, by downregulating ESRRA in a dose-dependent manner. In vivo, HGK reduced tumor growth with minimal toxicity, though high doses showed possible renal effects. IL-12 levels decreased, and EMT markers were altered. ESRRA was overexpressed in ESCC tissues and correlated with EMT-related genes. TCGA analysis confirmed ESRRA’s association with poor survival in ESCC patients.

Conclusion

HGK effectively suppresses ESCC with low toxicity, primarily by inhibiting ESRRA and blocking EMT, highlighting its therapeutic potential.

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羟基根宽素通过ESRRA信号通路在食管癌中的抗癌机制研究。

目的：探讨ESRRA在食管鳞状细胞癌（ESCC）进展中的作用，评价羟基根管素（HGK）的抗肿瘤作用，重点研究其与ESRRA的相互作用及其分子机制。方法：采用CCK-8法、Hoechst染色法、Transwell法和集落形成法对HGK处理的EC109和TE-1细胞进行细胞活力、凋亡、侵袭和增殖的评估。通过qPCR和Western blot分析ESRRA的表达。建立ESCC小鼠模型，给药组给予HGK。ELISA法检测血清IL-10、IL-12水平；用组织学方法评价肿瘤的生长和毒性。采用免疫组化（IHC）和RT-qPCR分析EMT标记的表达。TCGA数据库分析探讨了esrra相关通路及其与肿瘤微环境和患者生存的关系。结果：HGK通过下调ESRRA，以剂量依赖性的方式抑制EC109和TE-1细胞的增殖和迁移，特别是在EC109细胞中。在体内，HGK以最小的毒性降低肿瘤生长，尽管高剂量可能会对肾脏产生影响。IL-12水平降低，EMT标志物改变。ESRRA在ESCC组织中过表达，并与emt相关基因相关。TCGA分析证实ESRRA与ESCC患者生存差相关。结论：HGK主要通过抑制ESRRA和阻断EMT对ESCC具有低毒性的有效抑制作用，显示了其治疗潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Genetics ONCOLOGY-GENETICS & HEREDITY

CiteScore

3.20

自引率

5.30%

发文量

167

审稿时长

27 days

期刊介绍： The aim of Cancer Genetics is to publish high quality scientific papers on the cellular, genetic and molecular aspects of cancer, including cancer predisposition and clinical diagnostic applications. Specific areas of interest include descriptions of new chromosomal, molecular or epigenetic alterations in benign and malignant diseases; novel laboratory approaches for identification and characterization of chromosomal rearrangements or genomic alterations in cancer cells; correlation of genetic changes with pathology and clinical presentation; and the molecular genetics of cancer predisposition. To reach a basic science and clinical multidisciplinary audience, we welcome original full-length articles, reviews, meeting summaries, brief reports, and letters to the editor.