Scopoletin inhibits ovarian cancer progression by reducing glycolysis via the EGFR-AKT pathway

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2025-08-13 DOI:10.1016/j.tice.2025.103086

Xi Lin , Yingying He , Jingke Song , Xiaomin Xu , Jingui Xu , Kening Zhou , Lihua Zheng

{"title":"Scopoletin inhibits ovarian cancer progression by reducing glycolysis via the EGFR-AKT pathway","authors":"Xi Lin , Yingying He , Jingke Song , Xiaomin Xu , Jingui Xu , Kening Zhou , Lihua Zheng","doi":"10.1016/j.tice.2025.103086","DOIUrl":null,"url":null,"abstract":"<div><div>This study aimed to investigate the antitumor effects and mechanisms of scopoletin in chemoresistant ovarian cancer (OC) cells. Cell viability, migration, invasion, and the cell cycle were assessed. The effect of scopoletin on aerobic glycolysis was determined by measuring glucose uptake, lactate, ATP, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR). Bioinformatics was used to analyze the relationship between scopoletin and epidermal growth factor receptor (EGFR). The levels of p-EGFR and p-AKT were measured using western blotting. <em>In vivo</em> xenograft models were used to validate the role of scopoletin. These results revealed that scopoletin inhibited the viability, migration, invasion, and colony formation of chemoresistant OC cells. It induced concentration-dependent G1/S phase arrest and reversed aerobic glycolysis by reducing glucose uptake, lactate production, ATP levels, and ECAR while increasing the OCR. Scopoletin targets the EGFR-AKT axis and downregulates p-EGFR and p-AKT expression. Crucially, the combination of scopoletin and the EGFR inhibitor lapatinib synergistically inhibited cellular metabolic reprogramming and proliferation and significantly enhanced tumor growth inhibition in mice compared to single-drug treatment. In conclusion, scopoletin suppresses chemoresistant OC progression and metastasis by targeting the EGFR-AKT pathway. The synergistic effect of scopoletin and lapatinib demonstrates a promising therapeutic strategy for overcoming OC chemoresistance.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"97 ","pages":"Article 103086"},"PeriodicalIF":2.5000,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Tissue & cell","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0040816625003684","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ANATOMY & MORPHOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

This study aimed to investigate the antitumor effects and mechanisms of scopoletin in chemoresistant ovarian cancer (OC) cells. Cell viability, migration, invasion, and the cell cycle were assessed. The effect of scopoletin on aerobic glycolysis was determined by measuring glucose uptake, lactate, ATP, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR). Bioinformatics was used to analyze the relationship between scopoletin and epidermal growth factor receptor (EGFR). The levels of p-EGFR and p-AKT were measured using western blotting. In vivo xenograft models were used to validate the role of scopoletin. These results revealed that scopoletin inhibited the viability, migration, invasion, and colony formation of chemoresistant OC cells. It induced concentration-dependent G1/S phase arrest and reversed aerobic glycolysis by reducing glucose uptake, lactate production, ATP levels, and ECAR while increasing the OCR. Scopoletin targets the EGFR-AKT axis and downregulates p-EGFR and p-AKT expression. Crucially, the combination of scopoletin and the EGFR inhibitor lapatinib synergistically inhibited cellular metabolic reprogramming and proliferation and significantly enhanced tumor growth inhibition in mice compared to single-drug treatment. In conclusion, scopoletin suppresses chemoresistant OC progression and metastasis by targeting the EGFR-AKT pathway. The synergistic effect of scopoletin and lapatinib demonstrates a promising therapeutic strategy for overcoming OC chemoresistance.

查看原文本刊更多论文

东莨菪素通过EGFR-AKT通路减少糖酵解抑制卵巢癌进展

本研究旨在探讨东莨菪碱对化疗耐药卵巢癌（OC）细胞的抗肿瘤作用及其机制。评估细胞活力、迁移、侵袭和细胞周期。通过测定葡萄糖摄取、乳酸、ATP、细胞外酸化率（ECAR）和耗氧量（OCR）来确定东莨菪碱对有氧糖酵解的影响。采用生物信息学方法分析东莨菪素与表皮生长因子受体（EGFR）的关系。western blotting检测p-EGFR和p-AKT水平。采用体内异种移植模型验证东莨菪碱的作用。这些结果表明，东莨菪碱抑制化疗耐药OC细胞的活力、迁移、侵袭和集落形成。它诱导浓度依赖性G1/S期阻滞，通过降低葡萄糖摄取、乳酸生成、ATP水平和ECAR逆转有氧糖酵解，同时增加OCR。东莨菪素靶向EGFR-AKT轴，下调p-EGFR和p-AKT的表达。至关重要的是，与单药治疗相比，东莨菪碱和EGFR抑制剂拉帕替尼联合使用可协同抑制细胞代谢重编程和增殖，并显著增强小鼠肿瘤生长抑制。总之，东莨菪素通过靶向EGFR-AKT通路抑制化疗耐药OC的进展和转移。东莨菪碱和拉帕替尼的协同作用显示了克服卵巢癌化疗耐药的有希望的治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.