The cytotoxic effects of indoleamine 2, 3-dioxygenase inhibitors on triple negative breast cancer cells upon tumor necrosis factor ? stimulation
Küçük Resim Yok
Tarih
2023
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Wolters Kluwer Medknow Publications
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Context: Overexpressed indoleamine 2,3-dioxygenase (IDO) has been observed in many types of cancer and plays an essential role in the tumor microenvironment through immune cells function. Aims: In our study, the therapeutic potentials of two different IDO inhibitors (Epacadostat [EPA] and 1-methyl-L-tryptophan [L-1MT]) in triple-negative breast cancer (TNBC) cells were assessed with and without tumor necrosis factor-? (TNF-?) stimulation. Materials and Methods: The anticancer activity of EPA and L-1MT alone and in combination with TNF-? was analyzed by WST-1, annexin V, cell cycle analysis, and acridine orange/ethidium bromide staining. In addition, the relationship between IDO1 and programmed death-ligand 1 (PD-L1) expressions in TNBC cells upon treatment with IDO inhibitors was evaluated by reverse transcription-polymerase chain reaction analysis. Statistical Analysis Used: SPSS 22.0 was conducted for statistical analysis. The one-way analysis of variance with Tukey's multiple comparison test was performed for multiple groups. Independent (unpaired) t -test was used for the comparison of two groups. Results: EPA and L-1MT alone significantly suppressed the TNBC cell viability through the induction of apoptotic cell death and G0/G1 arrest (P < 0.05). TNF-? alone induced the overexpression of IDO1 and PD-L1 in TNBC cells compared with MCF-10A control cells. However, IDO inhibitors significantly inhibited overexpressed IDO1 mRNA levels. Furthermore, EPA alone and co-treated with TNF-? suppressed the mRNA level of PD-L1 in TNBC cells. Therefore, TNF-? stimulation enhanced the therapeutic effects of IDO inhibitors on TNBC. Conclusions: Our findings showed that the efficacy of IDO inhibitors was mediated by pro-inflammatory cytokine. However, different molecular signaling pathways are associated with pro-inflammatory cytokines production, and the expression of IDO1 and PD-L1 calls for further investigations. © 2022 Journal of Cancer Research and Therapeutics | Published by Wolters Kluwer - Medknow.
Açıklama
Anahtar Kelimeler
3-Dioxygenase, 3-Dioxygenase İnhibitors, Epacadostat, İndoleamine 2, İndoleamine 2, Triple-Negative Breast Cancer, Tumor Necrosis Factor-?
Kaynak
Journal of Cancer Research and Therapeutics
WoS Q Değeri
Scopus Q Değeri
Q3
Cilt
19
Sayı
8
