Mechanistic study of quercetin in the treatment of thyroid cancer with diabetes based on network pharmacology and in vitro experiments

IntroductionThyroid cancer (TC) stands as a prevalent malignancy within the global endocrine system, with its incidence notably exacerbated by the presence of diabetes. However, the specific relationship between TC and diabetes and promising treatment strategies that address both conditions simultan...

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Main Authors: Siyu Liu, Yujie Cai, Wenjing Chen, Xiao Yuan, Zhipeng He, Feng Lin
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2025.1537799/full
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author Siyu Liu
Siyu Liu
Siyu Liu
Yujie Cai
Wenjing Chen
Xiao Yuan
Xiao Yuan
Zhipeng He
Zhipeng He
Zhipeng He
Feng Lin
Feng Lin
author_facet Siyu Liu
Siyu Liu
Siyu Liu
Yujie Cai
Wenjing Chen
Xiao Yuan
Xiao Yuan
Zhipeng He
Zhipeng He
Zhipeng He
Feng Lin
Feng Lin
author_sort Siyu Liu
collection DOAJ
description IntroductionThyroid cancer (TC) stands as a prevalent malignancy within the global endocrine system, with its incidence notably exacerbated by the presence of diabetes. However, the specific relationship between TC and diabetes and promising treatment strategies that address both conditions simultaneously are still under exploration. Quercetin, herb medicine from traditional Chinese medicine (TCM), is widely used as an adjunctive therapy with Western medicine in the treatment of many diseases based on a wide range of biological effects. The objective of this study was to explore the efficacy of quercetin in treating TC with diabetes combining bioinformatics and network pharmacology.MethodsAfter multistep Cox proportional hazards regressions, we built a prognostic risk model for TC-diabetes and identified targets for quercetin in treating TC with diabetes. Molecular docking was employed to evaluate the binding affinities of quercetin with core targets, and in vitro experiments verified quercetin’s targets and functions.Results11 prognostic genes were included in the prediction model with a great performance in predicting the prognosis of TC-diabetic patients. 45 genes served as the targets of quercetin in treating TC with diabetes, among which, 5 core genes were screened as the most contributors. Through molecular docking, matrix metalloproteinase-3 (MMP3) was identified as the potential therapeutic target of quercetin. In vitro experiments have found that quercetin can inhibit the proliferation of thyroid cancer cells and the expression of MMP3 under high glucose conditions.DiscussionIn summary, quercetin may suppress the progression of TC-diabetes by inhibiting the proliferation of thyroid cancer cells and the expression of MMP3.
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spelling doaj-art-d8aaec97a9f044f8b93766be61c0c7912025-08-20T02:33:11ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-06-011610.3389/fendo.2025.15377991537799Mechanistic study of quercetin in the treatment of thyroid cancer with diabetes based on network pharmacology and in vitro experimentsSiyu Liu0Siyu Liu1Siyu Liu2Yujie Cai3Wenjing Chen4Xiao Yuan5Xiao Yuan6Zhipeng He7Zhipeng He8Zhipeng He9Feng Lin10Feng Lin11Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaAnhui Public Health Clinical Center, Hefei, ChinaDepartment of Radiology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, ChinaSchool of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, ChinaSchool of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, ChinaDepartment of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaAnhui Public Health Clinical Center, Hefei, ChinaDepartment of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaAnhui Public Health Clinical Center, Hefei, ChinaDepartment of General Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, ChinaDepartment of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaAnhui Public Health Clinical Center, Hefei, ChinaIntroductionThyroid cancer (TC) stands as a prevalent malignancy within the global endocrine system, with its incidence notably exacerbated by the presence of diabetes. However, the specific relationship between TC and diabetes and promising treatment strategies that address both conditions simultaneously are still under exploration. Quercetin, herb medicine from traditional Chinese medicine (TCM), is widely used as an adjunctive therapy with Western medicine in the treatment of many diseases based on a wide range of biological effects. The objective of this study was to explore the efficacy of quercetin in treating TC with diabetes combining bioinformatics and network pharmacology.MethodsAfter multistep Cox proportional hazards regressions, we built a prognostic risk model for TC-diabetes and identified targets for quercetin in treating TC with diabetes. Molecular docking was employed to evaluate the binding affinities of quercetin with core targets, and in vitro experiments verified quercetin’s targets and functions.Results11 prognostic genes were included in the prediction model with a great performance in predicting the prognosis of TC-diabetic patients. 45 genes served as the targets of quercetin in treating TC with diabetes, among which, 5 core genes were screened as the most contributors. Through molecular docking, matrix metalloproteinase-3 (MMP3) was identified as the potential therapeutic target of quercetin. In vitro experiments have found that quercetin can inhibit the proliferation of thyroid cancer cells and the expression of MMP3 under high glucose conditions.DiscussionIn summary, quercetin may suppress the progression of TC-diabetes by inhibiting the proliferation of thyroid cancer cells and the expression of MMP3.https://www.frontiersin.org/articles/10.3389/fendo.2025.1537799/fullquercetinthyroid cancerdiabetesnetwork pharmacologybioinformaticsmolecular docking
spellingShingle Siyu Liu
Siyu Liu
Siyu Liu
Yujie Cai
Wenjing Chen
Xiao Yuan
Xiao Yuan
Zhipeng He
Zhipeng He
Zhipeng He
Feng Lin
Feng Lin
Mechanistic study of quercetin in the treatment of thyroid cancer with diabetes based on network pharmacology and in vitro experiments
Frontiers in Endocrinology
quercetin
thyroid cancer
diabetes
network pharmacology
bioinformatics
molecular docking
title Mechanistic study of quercetin in the treatment of thyroid cancer with diabetes based on network pharmacology and in vitro experiments
title_full Mechanistic study of quercetin in the treatment of thyroid cancer with diabetes based on network pharmacology and in vitro experiments
title_fullStr Mechanistic study of quercetin in the treatment of thyroid cancer with diabetes based on network pharmacology and in vitro experiments
title_full_unstemmed Mechanistic study of quercetin in the treatment of thyroid cancer with diabetes based on network pharmacology and in vitro experiments
title_short Mechanistic study of quercetin in the treatment of thyroid cancer with diabetes based on network pharmacology and in vitro experiments
title_sort mechanistic study of quercetin in the treatment of thyroid cancer with diabetes based on network pharmacology and in vitro experiments
topic quercetin
thyroid cancer
diabetes
network pharmacology
bioinformatics
molecular docking
url https://www.frontiersin.org/articles/10.3389/fendo.2025.1537799/full
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