Changes in expression of TLR-4, TGF-β, INF-γ, TNF-α in cultured T24/83 cells of invasive bladder cancer treated with cisplatin and/or polyphenolic adjuvant melanin


  • P.G. Yakovlev Clinical Hospital “Feofaniya”, Center of Urology and Oncourology, Kyiv 03143, Ukraine
  • O.I. Gorbach National Cancer Institute, Kyiv 03022, Ukraine
  • N.M. Khranovska National Cancer Institute, Kyiv 03022, Ukraine
  • A.V. Beliayeva Taras Shevchenko National University of Kyiv
  • O.V. Skachkova National Cancer Institute, Kyiv 03022, Ukraine
  • T.D. Skaterna Palladin Institute of Biochemistry
  • L.G. Kalachniuk National University of Life and Environmental Sciences of Ukraine
  • L.I. Ostapchenko Taras Shevchenko National University of Kyiv
  • L.V. Garmanchuk Taras Shevchenko National University of Kyiv



apoptosis, cell line T24/83, INF-γ, invasive bladder cancer, melanin, TGFβ, TLR4, TNF, urothelial carcinoma


Background: Toll-like receptor 4 (TLR4) is known to be involved in carcinogenesis and cancer progression. Changes in TLR4 expression are associated with changes in the expression of key cellular cytokines (transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ)), which affect cancer progression and metastasis. Aim: To study changes in the expression of TLR4, TGF-β, TNF-α, IFN-γ genes, the level of apoptosis and cell cycle distribution in human invasive urothelial carcinoma T24/83 cells under the treatment with polyphenolic adjuvant compound of fungal origin melanin, cytotoxic drug cisplatin, and combination of both. Materials and Methods: T24/83 cells were incubated with cisplatin (0.05 mM), melanin (5 µg/ml), or their combination. The expression level of TLR-4, TGF-β, INF-γ, TNF-α was evaluated by the real time polymerase chain reaction. The flow cytometry was used to study cell cycle distribution, proliferative activity and level of apoptosis. Morphological analysis of the Т24/83 cells was performed as well. Results: Melanin, cisplatin, and their combination downregulate TLR4 expression (2.67; 1.28; and 2.73-fold decrease, respectively) and TNF-α expression (6.5; 1.4; and 1.7-fold decrease, respectively). Melanin did not affect TGF-β expression while cisplatin caused 13-fold downregulation of TGF-β. The combined use of cisplatin and melanin decreased TGF-β expression by 6.5 times. The upregulation of IFN-γ by melanin, cisplatin, and their combination was demonstrated (4.3; 6.7; and 2-fold increase, respectively). All treatment modalities increased the level of apoptosis in T24/83 cells. Melanin treatment increased significantly the proportion of fibroblast-like cells in T24/83 culture with decreased cell adhesion to the substrate. Conclusions: Melanin, cisplatin, and combination of both agents affect significantly TLR4, TNF-α, TGF-β, INF-γ expression, cell cycle distribution and morphology in T24/83 cells suggesting their transition to less aggressive phenotype.


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How to Cite

Yakovlev, P., Gorbach, O., Khranovska, N., Beliayeva, A., Skachkova, O., Skaterna, T., … Garmanchuk, L. (2023). Changes in expression of TLR-4, TGF-β, INF-γ, TNF-α in cultured T24/83 cells of invasive bladder cancer treated with cisplatin and/or polyphenolic adjuvant melanin. Experimental Oncology, 43(1), 7–14.



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