Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Jun 24, 2025; 16(6): 106197
Published online Jun 24, 2025. doi: 10.5306/wjco.v16.i6.106197
NOTCH1 combined with chemotherapy synergistically inhibits triple-negative breast cancer
Wen-Jia Chen, Hua-Tao Wu, Yang-Zheng Lan, Zheng Wu, Xin-Ning Yu, Wen-Ting Lin, Jing Liu
Wen-Jia Chen, Yang-Zheng Lan, Zheng Wu, Jing Liu, The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
Hua-Tao Wu, Xin-Ning Yu, Department of General Surgery, First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
Wen-Ting Lin, Department of Pathology, Shantou University Medical College, Shantou 515041, Guangdong Province, China
Co-first authors: Wen-Jia Chen and Hua-Tao Wu.
Author contributions: Chen WJ and Wu HT contribute equally to this study as co-first authors; Chen WJ responsible for bioscientific experiments, data base screening, figure preparation, study designation, and paper drafting; Wu HT responsible for bioscientific experiments, statistical analysis, and paper drafting; Lan YZ responsible for statistical analysis; Yu XN and Wu Z responsible for collecting and organizing raw data and figure preparation; Lin WT responsible for image quality control; Liu J responsible for study designation, supervising the project, statistical analysis, revising and polishing the whole study and the manuscript, and image quality control; all authors reviewed the manuscript and approved the submitted version.
Supported by National Natural Science Foundation of China, No. 82273457; the Natural Science Foundation of Guangdong Province, No. 2021A1515012180 and No. 2023A1515012762; Science and Technology Special Project of Guangdong Province, No. 210715216902829 and No. 200628175260810; and ‘Dengfeng Project’ for the Construction of High-Level Hospitals in Guangdong Province—First Affiliated Hospital of Shantou University College Supporting Funding, No. 202003-10.
Institutional animal care and use committee statement: The Animal Ethics Committee of Shantou University Medical College, Shantou, China, approved the protocol for the animal experiment. All animals received care as prescribed under the ‘Guide for the Care and Use of Laboratory Animals’.
Conflict-of-interest statement: The authors declare that they have no competing interests.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jing Liu, MD, PhD, Associate Professor, The Breast Center, Cancer Hospital of Shantou University Medical College, No. 7 Raoping Road, Shantou 515041, Guangdong Province, China. jliu12@stu.edu.cn
Received: February 19, 2025
Revised: April 3, 2025
Accepted: May 7, 2025
Published online: June 24, 2025
Processing time: 121 Days and 16.5 Hours
Abstract
BACKGROUND

Chemotherapy for triple-negative breast cancer (TNBC) is often limited in efficacy due to drug resistance. The NOTCH1 pathway significantly contributes to the advancement of tumors, but its mechanism of action in sensitizing TNBC to chemotherapy and its association with the downstream molecule, NT5E, is unclear.

AIM

To explore the molecular mechanisms by which NOTCH1 regulates cisplatin sensitivity in TNBC cells, and to validate its synergistic effect with NT5E.

METHODS

Expression of NOTCH1 in MDA-MB-231 cells was silenced using RNA interference, and the changes in cell proliferation, migration and cisplatin sensitivity were measured in combination with cell function experiments. The regulatory relationship between NOTCH1 and NT5E was analyzed using qPCR and Western blotting, and the silencing effect of NOTCH1 was verified using NT5E overexpression experiments.

RESULTS

Knockdown of NOTCH1 hindered the growth and motility of TNBC cells and lowered cisplatin’s half-maximal inhibitory concentration. Expression of NOTCH1 and NT5E was positively correlated, and NOTCH1 silencing led to a decrease in the expression of NT5E. Elevated NT5E expression attenuated the suppressive effects of NOTCH1 knockdown on both cell proliferation and cisplatin response.

CONCLUSION

NOTCH1 enhances TNBC cisplatin chemosensitivity by regulating NT5E expression. This study provides a new target and experimental basis for the development of combination therapy strategies for TNBC.

Keywords: NOTCH1; Triple-negative breast cancer; Cisplatin; Sensitivity; NT5E

Core Tip: Chemoresistance in triple-negative breast cancer (TNBC) hampers chemotherapy effectiveness. This study shows that targeting NOTCH1 reduced cell proliferation and migration, enhancing cisplatin sensitivity. A positive correlation between NOTCH1 and NT5E expression was observed, with NT5E contributing to tumor progression and chemoresistance. NOTCH1 silencing downregulated NT5E, while NT5E overexpression partially reversed these effects. These findings suggest that targeting the NOTCH1-NT5E pathway could improve chemotherapy outcomes in TNBC.