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

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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