AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO025080037
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ORIGINAL RESEARCH ARTICLE

Tetramethyl thyroxine promotes bladder cancer development by regulating the expression of integrin αV, VEGF, and TP53

Wenjing Zhang1† ,  Rui Guo1† ,  Xiaoyang Chen1 ,  Ruolan Chen1 ,  Jian Dong1 ,  Yan Liu1 ,  Danning Song1 ,  Shangyang Pan1 ,  Zhao Yang1* ,  Jianfeng Wang2*
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1 College of Life Science and Technology, State Key Laboratory of Green Biomanufacturing, Innovation Center of Molecular Diagnostics, Beijing University of Chemical Technology, Beijing, China
2 Department of Urology, China-Japan Friendship Hospital, Beijing, China
EJMO, 025080037 https://doi.org/10.36922/EJMO025080037
Submitted: 21 February 2025 | Revised: 30 March 2025 | Accepted: 2 April 2025 | Published: 17 April 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Bladder cancer (BC) is the most prevalent malignancy of the genitourinary system, exhibiting the highest morbidity and mortality rates among cancers in this category. Tetramethyl thyroxine (T4) has been recognized to promote the proliferation of various cancer cells. However, the possible effect and underlying mechanisms of T4 on the onset and progression of BC remain to be fully elucidated. Our research demonstrated that T4 significantly promoted the proliferation and migration of EJ-1 and T24 cells. The proliferation of T24 and EJ-1 cells increased by 5 – 28.3% and 4.7 – 18.7%, respectively. Similarly, the scratch healing rates of T24 and EJ-1 cells increased by 9.27 – 41.01% and 11.47 – 35.8%, respectively. In addition, apoptosis of T24 and EJ-1 cells was also significantly reduced after T4 treatment. Furthermore, in vivo xenograft tumor model further corroborated that T4 facilitated the growth of EJ-1 cell-derived tumors. Our findings indicated that T4 promoted tumor angiogenesis and cell proliferation by upregulating its receptor integrin αV and vascular endothelial growth factor, while simultaneously suppressed the expression of the tumor suppressor protein TP53. Collectively, our research has determined the tumor-promoting effect and molecular mechanism of T4 on BC through cell and animal models. In the future, by further expanding the sample size and pre-clinical design, it is expected to provide new theoretical foundations and potential targets for the prevention, diagnosis, and treatment of BC.

Keywords
Bladder cancer
Tetramethyl thyroxine
Proliferation
Migration
Integrin αV
Funding
Funding was received for the research, authorship, and/ or publication of this article. This work was supported by the Major Research Plan of the National Natural Science Foundation of China (92359202), National Key Research and Development Program (2024YFC3405500), “Open Competition to Select the Best Candidates” Key Technology Program for Nucleic Acid Drugs of NCTIB (NCTIB2022HS01016), and the Joint Project of Biomedical Translational Engineering Research Center of Beijing University of Chemical Technology-China-Japan Friendship Hospital (XK2023-21).
Conflict of interest
The authors declare that no commercial or financial conflicts of interest were identified in this research.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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