Matrine Inhibits Breast Cancer Cell Proliferation and Epithelial-Mesenchymal Transition Through Regulating the LINC01116/miR-9-5p/ITGB1 Axis

Background: Breast cancer (BC) is the most prevalent solid cancer affecting women’s health globally. Matrine (MAT), a traditional Chinese herb, has exhibited antitumor effects against BC. However, its mechanism of action, particularly whether it involves the control of cell proliferation and epithel...

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Main Authors: Lili Ren, Ziru Fang, Jiaojiao Xu, Xiaoxiao Wu, Yongjun Zhang, Hu Cai, Zhicun Han
Format: Article
Language:English
Published: Galenos Publishing House 2025-01-01
Series:Balkan Medical Journal
Online Access:https://balkanmedicaljournal.org/text.php?lang=en&id=2670
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author Lili Ren
Ziru Fang
Jiaojiao Xu
Xiaoxiao Wu
Yongjun Zhang
Hu Cai
Zhicun Han
author_facet Lili Ren
Ziru Fang
Jiaojiao Xu
Xiaoxiao Wu
Yongjun Zhang
Hu Cai
Zhicun Han
author_sort Lili Ren
collection DOAJ
description Background: Breast cancer (BC) is the most prevalent solid cancer affecting women’s health globally. Matrine (MAT), a traditional Chinese herb, has exhibited antitumor effects against BC. However, its mechanism of action, particularly whether it involves the control of cell proliferation and epithelial-mesenchymal transition (EMT), remains unknown. Aims: To explore MAT’s role in BC and its regulatory mechanisms, as well as to identify targets for the development of novel medicines and improvement of BC treatment modalities. Study Design: Experimental study. Methods: The UALCAN and Lnc2Cancer 3.0 databases were used to predict the expression of LINC01116 in BC. The BC cells (MDA-MB-231 and MCF-7) were treated with various concentrations of MAT, and the optimal dose and timing of MAT action were determined using CCK-8 and quantitative real-time polymerase chain reaction assays. Functional assays such as CCK-8, EdU, Transwell, Western blot, and flow cytometry assays were performed on the BC cells, and the impacts of LINC01116, miR-9-5p, and ITGB1 expression levels on MAT’s mechanism of action were assessed. The association between LINC01116, miR-9-5p, and ITGB1 was evaluated using dual luciferase and RNA immunoprecipitation assays. Furthermore, the size and weight of the subcutaneous tumors in mice model were assessed. The effect of LINC01116 overexpression on the in vivo action of MAT and histopathological staining (TUNEL immunofluorescence, hematoxylin & eosin staining, immunohistochemistry staining for Ki67 and Bax) were also assessed. Results: The optimal dose and duration of MAT administration were 8 µm and 24 h, respectively. MAT effectively inhibited BC cell proliferation, EMT progression, and biological functions, while promoting BC cell apoptosis. The animal model experiments also demonstrated that MAT inhibited BC tumor growth in vivo. Furthermore, MAT inhibited LINC01116, which acted as a sponge for miR-9-5p, increasing the ITGB1 level. Conclusion: MAT suppresses BC cell and EMT proliferation via the LINC01116/miR-9-5p/ITGB1 pathway. Thus, MAT may be a promising target for adjuvant anti-BC therapy.
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spelling doaj-art-20f0fd893d50406d90d39e5bf0722d372025-01-07T12:55:07ZengGalenos Publishing HouseBalkan Medical Journal2146-31232146-31312025-01-01421546510.4274/balkanmedj.galenos.2024.2024-8-49Matrine Inhibits Breast Cancer Cell Proliferation and Epithelial-Mesenchymal Transition Through Regulating the LINC01116/miR-9-5p/ITGB1 AxisLili Ren0https://orcid.org/0000-0003-3766-2350Ziru Fang1https://orcid.org/0000-0002-9858-5742Jiaojiao Xu2https://orcid.org/0000-0001-5436-3059Xiaoxiao Wu3https://orcid.org/0009-0000-7455-504XYongjun Zhang4https://orcid.org/0000-0002-2326-7870Hu Cai5https://orcid.org/0000-0002-9178-5960Zhicun Han6https://orcid.org/0000-0003-0507-0203Department of Integration of Traditional Chinese and Western Medicine, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Medical Sciences, Hangzhou, Zhejiang 310022, ChinaDepartment of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, ChinaDepartment of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, ChinaDepartment of Pathology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, ChinaDepartment of Integration of Traditional Chinese and Western Medicine, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Medical Sciences, Hangzhou, Zhejiang 310022, ChinaDepartment of Integration of Traditional Chinese and Western Medicine, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Medical Sciences, Hangzhou, Zhejiang 310022, ChinaDepartment of Acupuncture, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310022, ChinaBackground: Breast cancer (BC) is the most prevalent solid cancer affecting women’s health globally. Matrine (MAT), a traditional Chinese herb, has exhibited antitumor effects against BC. However, its mechanism of action, particularly whether it involves the control of cell proliferation and epithelial-mesenchymal transition (EMT), remains unknown. Aims: To explore MAT’s role in BC and its regulatory mechanisms, as well as to identify targets for the development of novel medicines and improvement of BC treatment modalities. Study Design: Experimental study. Methods: The UALCAN and Lnc2Cancer 3.0 databases were used to predict the expression of LINC01116 in BC. The BC cells (MDA-MB-231 and MCF-7) were treated with various concentrations of MAT, and the optimal dose and timing of MAT action were determined using CCK-8 and quantitative real-time polymerase chain reaction assays. Functional assays such as CCK-8, EdU, Transwell, Western blot, and flow cytometry assays were performed on the BC cells, and the impacts of LINC01116, miR-9-5p, and ITGB1 expression levels on MAT’s mechanism of action were assessed. The association between LINC01116, miR-9-5p, and ITGB1 was evaluated using dual luciferase and RNA immunoprecipitation assays. Furthermore, the size and weight of the subcutaneous tumors in mice model were assessed. The effect of LINC01116 overexpression on the in vivo action of MAT and histopathological staining (TUNEL immunofluorescence, hematoxylin & eosin staining, immunohistochemistry staining for Ki67 and Bax) were also assessed. Results: The optimal dose and duration of MAT administration were 8 µm and 24 h, respectively. MAT effectively inhibited BC cell proliferation, EMT progression, and biological functions, while promoting BC cell apoptosis. The animal model experiments also demonstrated that MAT inhibited BC tumor growth in vivo. Furthermore, MAT inhibited LINC01116, which acted as a sponge for miR-9-5p, increasing the ITGB1 level. Conclusion: MAT suppresses BC cell and EMT proliferation via the LINC01116/miR-9-5p/ITGB1 pathway. Thus, MAT may be a promising target for adjuvant anti-BC therapy.https://balkanmedicaljournal.org/text.php?lang=en&id=2670
spellingShingle Lili Ren
Ziru Fang
Jiaojiao Xu
Xiaoxiao Wu
Yongjun Zhang
Hu Cai
Zhicun Han
Matrine Inhibits Breast Cancer Cell Proliferation and Epithelial-Mesenchymal Transition Through Regulating the LINC01116/miR-9-5p/ITGB1 Axis
Balkan Medical Journal
title Matrine Inhibits Breast Cancer Cell Proliferation and Epithelial-Mesenchymal Transition Through Regulating the LINC01116/miR-9-5p/ITGB1 Axis
title_full Matrine Inhibits Breast Cancer Cell Proliferation and Epithelial-Mesenchymal Transition Through Regulating the LINC01116/miR-9-5p/ITGB1 Axis
title_fullStr Matrine Inhibits Breast Cancer Cell Proliferation and Epithelial-Mesenchymal Transition Through Regulating the LINC01116/miR-9-5p/ITGB1 Axis
title_full_unstemmed Matrine Inhibits Breast Cancer Cell Proliferation and Epithelial-Mesenchymal Transition Through Regulating the LINC01116/miR-9-5p/ITGB1 Axis
title_short Matrine Inhibits Breast Cancer Cell Proliferation and Epithelial-Mesenchymal Transition Through Regulating the LINC01116/miR-9-5p/ITGB1 Axis
title_sort matrine inhibits breast cancer cell proliferation and epithelial mesenchymal transition through regulating the linc01116 mir 9 5p itgb1 axis
url https://balkanmedicaljournal.org/text.php?lang=en&id=2670
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