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IDO1 Modulates the Sensitivity of Epithelial Ovarian Cancer Cells to Cisplatin through ROS/p53-Dependent Apoptosis.
- Source :
- International Journal of Molecular Sciences; Oct2022, Vol. 23 Issue 19, p12002, 13p
- Publication Year :
- 2022
-
Abstract
- Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-containing dioxygenase that may play a part in chemoresistance in ovarian cancer. However, its role in cisplatin (DDP) resistance is unclear. Here, the expression level of IDO1 in tumors in platinum-resistant (n = 22) and -sensitive (n = 46) ovarian cancer patients was determined, and then how IDO1 modulated DDP resistance was explored in vitro and in vivo. The IDO1 expression level in platinum-resistant patients was higher than that in -sensitive patients, and a higher IDO1 level was correlated with poor prognosis in type II cancer patients. Up-regulating IDO1 decreased DDP-induced apoptosis in SKOV3 cells via inhibiting the ROS/p53 cell-death pathway, thereby attenuating cytotoxicity of DDP. Silencing IDO1 enhanced p53-dependent apoptosis by increasing ROS accumulation, thereby enhancing DDP against SKOV3 cells. Down-knocking IDO1 augmented the action of DDP in vivo. These data demonstrated that silencing IDO1 enhanced the efficacy of DDP by intensifying p53-dependent apoptosis, and that targeting IDO1 can be a strategy to modulate DDP-based chemotherapy for epithelial ovarian cancer. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 16616596
- Volume :
- 23
- Issue :
- 19
- Database :
- Complementary Index
- Journal :
- International Journal of Molecular Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 159681700
- Full Text :
- https://doi.org/10.3390/ijms231912002