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
| Autor: | T. D. Skaterna, L. V. Garmanchuk, N. M. Khranovska, O V Skachkova, O I Gorbach, L G Kalachniuk, A V Beliayeva, Liudmyla Ostapchenko, P G Yakovlev |
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| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
Antineoplastic Agents medicine.disease_cause Melanin Interferon-gamma Downregulation and upregulation Transforming Growth Factor beta Interferon Cell Line Tumor medicine Humans Melanins Cisplatin Carcinoma Transitional Cell Tumor Necrosis Factor-alpha Chemistry Cell cycle Toll-Like Receptor 4 Urinary Bladder Neoplasms Oncology Apoptosis Cancer research Tumor necrosis factor alpha Carcinogenesis medicine.drug |
| Zdroj: | Experimental Oncology. |
| ISSN: | 2312-8852 1812-9269 |
| DOI: | 10.32471/exp-oncology.2312-8852.vol-43-no-1.15739 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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