Наукові публікації університету

Immunological hallmarks of cis-DDP-resistant Lewis lung carcinoma cells

Purpose: Tumor cell resistance to platinum-based chemotherapeutic agents is one of the major hurdles to successful cancer treatment with these drugs, and is associated with alterations in tumor cell immune evasion and immunomodulatory properties. Immunocyte targeting is considered as a relevant approach to fight drug-resistant cancer. In this study, immunological hallmarks of cis-DDP-resistant Lewis lung carcinoma cells (LLC/R9) were investigated. Methods: Immunological features of LLC/R9 cells cultured in vitro in normoxic and hypoxic conditions as well as of those that were grown in vivo were examined. The expression of immunologically relevant genes was evaluated by RT-PCR. Tumor cell susceptibility to the macrophage contact tumoricidal activity and NK-mediated cytolysis was investigated in MTT test. TNF-α-mediated tumor cell apoptosis as well as macrophage phagocytosis, oxidative metabolism, and CD206 expression after the treatment with conditioned media from normoxic and hypoxic tumor cells were studied by flow cytometry. Flow cytometry was also used to characterize dendritic cell maturity. Results: When growing in vitro, LLC/R9 were characterized by slightly increased immunosuppressive cytokine gene expression. Transition to in vivo growth was associated with the enhancement of transcription of these genes in tumor cells. LLC/R9 cells had lowered sensitivity to contact-dependent macrophage-mediated cytotoxicity and to the TNFα-mediated apoptosis in vitro. Conditioned media from hypoxic LLC/R9 cells stimulated reactive oxygen species generation and CD206 expression in non-sensitized macrophages. Acquisition of drug resistance by LLC/R9 cells was associated with their increased sensitivity to NK-cell-mediated cytolysis. Meanwhile, the treatment of LLCR/9-bearing animals with generated ex vivo and loaded with LLC/R9 cell-lysate dendritic cells (DCs) resulted in profoundly enhanced tumor metastasizing. Conclusion: Decreased sensitivity to macrophage cytolysis, polarizing effect on DCs maturation along with increased susceptibility to NK-cell cytotoxic action promote extensive local growth of chemoresistant LLC/R9 tumors in vivo, but hamper their metastasizing. © 2017, Springer-Verlag GmbH Germany, part of Springer Nature.

ID: 236525
Кількість показів: 33
дата змінення: 07.11.2019 14:11:36
Ким змінено (ім'я): (bio_36) Марія Рудик
Вид роботи:  Наукова публікація
Тип роботи:  Наукова стаття
Кількість сторінок:  13
Рік видання:  2018
Звітний рік:  2019
Видання:  Cancer Chemotherapy and Pharmacology
Том:  81
Випуск, частина:  2
Номери сторінок:  373-385
Галузь науки:  Фармакологія
Автори,співробітники Університету:  Сківка Лариса Михайлівна / Сенчило Наталія Василівна / Рудик Марія Петрівна
Автори зовнішні:  Федорчук Олександр Григорович /  Сусак Ярослав Михайлович  / Храновська Наталія Миколаївна / Скачкова Оксана Володимирівна
Кафедра / Відділ:  Кафедра мікробіології та імунології
Ключові слова:  Chemoresistancecis-DDP, Dendritic cells, Lewis lung carcinoma, Macrophage-mediated cytotoxicity, NK-cell-mediated cytolysis
Опубліковано за рішенням Вченої ради:  ні
Інститут/Факультет:  ННЦ "Інститут біології та медицини"

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