Morin inhibits the progression of 5-fluorouracil–resistant colorectal cancer by suppressing autophagy

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology Pub Date : 2025-04-24 DOI:10.1016/j.biocel.2025.106783

Rui Li , Fengxia Wang , Lu Huang , Lvheng Zhao , Ting Qin , Shan Liu , Kunyao Xu , Bi Wang , Ling Li , Sha He

{"title":"Morin inhibits the progression of 5-fluorouracil–resistant colorectal cancer by suppressing autophagy","authors":"Rui Li , Fengxia Wang , Lu Huang , Lvheng Zhao , Ting Qin , Shan Liu , Kunyao Xu , Bi Wang , Ling Li , Sha He","doi":"10.1016/j.biocel.2025.106783","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Resistance to 5-fluorouracil (5-FU) poses a significant challenge in colorectal cancer (CRC) treatment. Morin is a flavonoid with anti-tumor properties. However, its role in overcoming acquired 5-FU resistance in CRC remains unclear.</div></div><div><h3>Methods</h3><div>5-FU-resistant CRC (5-FU/CRC) cell lines (HT29/5-FU and HCT116/5-FU) were established using the IC50 concentration increment method. After treatment with Morin and autophagy inhibitors (3-MA) or agonists (RAPA), cell viability, apoptosis, colony formation, migration, invasion, and autophagy were evaluated. <em>In vivo</em>, xenograft models of 5-FU/CRC assessed Morin's therapeutic effects.</div></div><div><h3>Results</h3><div>5-FU/CRC cells were successfully constructed. Morin inhibited the viability, migration, and invasion of 5-FU/CRC cells and promoted apoptosis. Morin also inhibited autophagy in 5-FU/CRC cells. Besides, autophagy activated by RAPA could eliminate the effect of Morin on 5-FU/CRC cells, while 3-MA enhanced the effects of Morin. In nude mouse models, Morin inhibited the growth and improved the pathological structure of 5-FU/CRC xenografts by inhibiting autophagy.</div></div><div><h3>Conclusion</h3><div>Morin suppresses the progression of 5-FU/CRC by inhibiting autophagy, suggesting its potential as a therapeutic agent to combat 5-FU resistance.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"185 ","pages":"Article 106783"},"PeriodicalIF":3.4000,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Biochemistry & Cell Biology","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1357272525000500","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Resistance to 5-fluorouracil (5-FU) poses a significant challenge in colorectal cancer (CRC) treatment. Morin is a flavonoid with anti-tumor properties. However, its role in overcoming acquired 5-FU resistance in CRC remains unclear.

Methods

5-FU-resistant CRC (5-FU/CRC) cell lines (HT29/5-FU and HCT116/5-FU) were established using the IC50 concentration increment method. After treatment with Morin and autophagy inhibitors (3-MA) or agonists (RAPA), cell viability, apoptosis, colony formation, migration, invasion, and autophagy were evaluated. In vivo, xenograft models of 5-FU/CRC assessed Morin's therapeutic effects.

Results

5-FU/CRC cells were successfully constructed. Morin inhibited the viability, migration, and invasion of 5-FU/CRC cells and promoted apoptosis. Morin also inhibited autophagy in 5-FU/CRC cells. Besides, autophagy activated by RAPA could eliminate the effect of Morin on 5-FU/CRC cells, while 3-MA enhanced the effects of Morin. In nude mouse models, Morin inhibited the growth and improved the pathological structure of 5-FU/CRC xenografts by inhibiting autophagy.

Conclusion

Morin suppresses the progression of 5-FU/CRC by inhibiting autophagy, suggesting its potential as a therapeutic agent to combat 5-FU resistance.

查看原文本刊更多论文

桑辣素通过抑制自噬抑制5-氟尿嘧啶耐药结直肠癌的进展

背景：5-氟尿嘧啶（5-FU）耐药性是结直肠癌（CRC）治疗中的一个重大挑战。桑辣素是一种具有抗肿瘤特性的类黄酮。然而，其在克服CRC获得性5-FU耐药中的作用尚不清楚。方法采用IC50浓度递增法建立5-FU耐药CRC （5-FU/CRC）细胞株HT29/5-FU和HCT116/5-FU。用桑里素和自噬抑制剂（3-MA）或激动剂（RAPA）治疗后，评估细胞活力、凋亡、菌落形成、迁移、侵袭和自噬。在体内，5-FU/CRC异种移植模型评估了Morin的治疗效果。结果成功构建了5- fu /CRC细胞。桑辣素抑制5-FU/CRC细胞的活力、迁移和侵袭，促进细胞凋亡。桑辣素还能抑制5-FU/CRC细胞的自噬。此外，RAPA激活的自噬可以消除Morin对5-FU/CRC细胞的作用，而3-MA可以增强Morin的作用。在裸鼠模型中，桑里素通过抑制自噬来抑制5-FU/CRC异种移植物的生长，改善其病理结构。结论桑辣素通过抑制自噬抑制5-FU/CRC的进展，提示其可能是一种对抗5-FU耐药性的治疗药物。

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

International Journal of Biochemistry & Cell Biology 生物-生化与分子生物学

CiteScore

8.10

自引率

0.00%

发文量

124

审稿时长

19 days

期刊介绍： IJBCB publishes original research articles, invited reviews and in-focus articles in all areas of cell and molecular biology and biomedical research. Topics of interest include, but are not limited to: -Mechanistic studies of cells, cell organelles, sub-cellular molecular pathways and metabolism -Novel insights into disease pathogenesis -Nanotechnology with implication to biological and medical processes -Genomics and bioinformatics