ЗМІНИ ЕКСПРЕСІЇ TLR-4, TGF-β, INF-γ, TNF-α В КУЛЬТУРІ КЛІТИН T24/83 ІНВАЗИВНОГО РАКУ СЕЧОВОГО МІХУРА ПІД ДІЄЮ ЦИСПЛАТИНУ ТА/АБО ПОЛІФЕНОЛЬНОГО АД’ЮВАНТУ МЕЛАНІНУ

• Дата: 2023
• Автори: Yakovlev, P.G., Gorbach, O.I., Khranovska, N.M., Beliayeva, A.V., Skachkova, O.V., Skaterna, T.D., Kalachniuk, L.G., Ostapchenko, L.I., Garmanchuk, L.V.
• Формат: Стаття
• Мова: English
• Опубліковано: PH Akademperiodyka 2023
• Теми: меланін; уротеліальна карцинома; клітинна лінія T24/83; інвазивний рак сечового міхура; TLR4; TGF-β; INF-γ; TNF-α; апоптоз.
• Онлайн доступ: https://exp-oncology.com.ua/index.php/Exp/article/view/2021-1-8
• Назва журналу: Experimental Oncology

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.