IDO1 Modulates the Sensitivity of Epithelial Ovarian Cancer Cells to Cisplatin through ROS/p53-Dependent Apoptosis
Abstract
:1. Introduction
2. Results
2.1. A High IDO1 Level in Cancer Tissues Was Associated with Platinum-Resistance and Poor Prognosis in Type II Ovarian Cancer
2.2. A High Level of IDO1 Reduced DDP-Induced Apoptosis via Down-Regulation of the ROS/p53 Pathway
2.3. Silencing IDO1 Enhanced DDP through Activation of ROS/p53-Dependent Apoptois in SKOV3 Cells
2.4. Inhibition of IDO1 Improved the Anticancer Efficacy of DDP In Vivo
3. Discussion
4. Materials and Methods
4.1. Patients and Cancer Samples
4.2. Detection of IDO1 in Cancer Tissues with an Immunohistochemistry (IHC) Assay
4.3. Cells
4.4. Cell Transfection
4.5. In Vitro Treatments
4.6. Cell Viability
4.7. Apoptosis and Cell Cycle Analyses
4.8. Intracellular ROS
4.9. Mitochondrial Membrane Potential (MMP)
4.10. Determination of Kyn in Culture Supernatants
4.11. Determination of γ-H2AX by Immunofluorescence
4.12. Western Blot
4.13. In Vivo Therapies on Subcutaneous Tumors in Nude Mice
4.14. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
DAPI | 4′,6-diamidino-2-phenylindole |
DDP | cis-dichlorodiamineplatinum (II), cisplatin |
DSB | double-strand DNA break |
Bax | Bcl-2 associated X protein |
IDO1 | indoleamine 2,3-dioxygenase 1 |
IFN-γ | interferon-γ |
IHC | immunohistochemistry |
Kyn | l-kynurenine |
PFI | platinum-free interval |
PFS | progression-free survival |
PUMA | p53 upregulated modulator of apoptosis |
ROS | reactive oxygen species |
Trp | tryptophan |
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Clinicopathological Features | Case No. | IDO1 Expression Level | p Value | |
---|---|---|---|---|
Low (n = 33) | High (n = 35) | |||
Age (year) | 0.492 | |||
<50 | 24 | 13 (54.2%) | 11 (45.8%) | |
≥50 | 44 | 20 (45.5%) | 24 (54.5%) | |
Histological type | 0.012 * | |||
Serous | 54 | 22 (40.7%) | 32 (59.3%) | |
Others | 14 | 11 (78.6%) | 3 (21.4%) | |
Pathological grade | 0.447 | |||
G1 | 2 | 2 (100.0%) | 0 (0.0%) | |
G2 + G3 | 66 | 31 (47.0%) | 35 (53.0%) | |
Classification | 0.201 | |||
Type I | 16 | 10 (62.5%) | 6 (37.5%) | |
Type II | 52 | 23 (44.2%) | 29 (55.8%) | |
FIGO stage | 0.140 | |||
I/II | 21 | 13 (61.9%) | 8 (38.1%) | |
III/IV | 47 | 20 (42.6%) | 27 (57.4%) | |
Platinum response | 0.015 * | |||
Resistant | 22 | 6 (27.3%) | 16 (72.7%) | |
Sensitive | 46 | 27 (58.7%) | 19 (41.3%) |
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Wang, H.; Luo, Y.; Ran, R.; Li, X.; Ling, H.; Wen, F.; Yu, T. IDO1 Modulates the Sensitivity of Epithelial Ovarian Cancer Cells to Cisplatin through ROS/p53-Dependent Apoptosis. Int. J. Mol. Sci. 2022, 23, 12002. https://doi.org/10.3390/ijms231912002
Wang H, Luo Y, Ran R, Li X, Ling H, Wen F, Yu T. IDO1 Modulates the Sensitivity of Epithelial Ovarian Cancer Cells to Cisplatin through ROS/p53-Dependent Apoptosis. International Journal of Molecular Sciences. 2022; 23(19):12002. https://doi.org/10.3390/ijms231912002
Chicago/Turabian StyleWang, Houmei, Yuanyuan Luo, Rui Ran, Xinya Li, Hongjian Ling, Fang Wen, and Tinghe Yu. 2022. "IDO1 Modulates the Sensitivity of Epithelial Ovarian Cancer Cells to Cisplatin through ROS/p53-Dependent Apoptosis" International Journal of Molecular Sciences 23, no. 19: 12002. https://doi.org/10.3390/ijms231912002