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IFNγ enhances ferroptosis by increasing JAK‑STAT pathway activation to suppress SLCA711 expression in adrenocortical carcinoma

  • Authors:
    • Xinbo Yu
    • Dandan Zhu
    • Bixian Luo
    • Wei Kou
    • Yuling Cheng
    • Yu Zhu
  • View Affiliations / Copyright

    Affiliations: Department of Urology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China, Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
    Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 97
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    Published online on: March 23, 2022
       https://doi.org/10.3892/or.2022.8308
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Abstract

Adrenocortical carcinoma (ACC) is a rare type of tumor with a poor prognosis. Ferroptosis is a relatively novel form of programmed cell death driven by iron‑dependent lipid peroxidation accumulation. Recent evidence suggests that IFNγ facilitates erastin‑induced ferroptosis, which contributed to anticancer therapy in various types of cancer. However, it has remained elusive whether the regulation of IFNγ on ferroptosis has a positive role in the treatment of ACC. Thus, the aim of the present study was to explore the effects of IFNγ on erastin‑induced ferroptosis in the ACC cell line NCI‑H295R and investigate the underlying mechanisms. Cell viability was assessed using a Cell Counting Kit‑8 assay, an ethynyldioxyuridine proliferation assay and Live/Dead staining. The levels of iron, reactive oxygen species, lipid peroxidation and mitochondrial damage were also assessed. Western blot and reverse transcription‑quantitative PCR analyses were used to determine the underlying molecular mechanisms involved in the erastin‑induced ferroptosis of NCI‑H295R cells. The results suggested that IFNγ promoted erastin‑induced ferroptotic cell death. Furthermore, IFNγ enhanced erastin‑induced ferroptosis, as evidenced by the accumulation of iron, as well as the increase in lipid peroxidation and promotion of mitochondrial damage. Further analysis suggested that IFNγ enhanced ferroptosis by suppressing the expression of solute carrier family 7 member 11, an important negative regulator of ferroptosis, and this was achieved via activation of the JAK/STAT pathway in NCI‑H295R cells. The present study provided experimental evidence on the activity and mechanism of ferroptosis enhanced by IFNγ in ACC and may give critical insight into the immunotherapeutic management of ACC.
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Copy and paste a formatted citation
Spandidos Publications style
Yu X, Zhu D, Luo B, Kou W, Cheng Y and Zhu Y: IFNγ enhances ferroptosis by increasing JAK‑STAT pathway activation to suppress SLCA711 expression in adrenocortical carcinoma. Oncol Rep 47: 97, 2022.
APA
Yu, X., Zhu, D., Luo, B., Kou, W., Cheng, Y., & Zhu, Y. (2022). IFNγ enhances ferroptosis by increasing JAK‑STAT pathway activation to suppress SLCA711 expression in adrenocortical carcinoma. Oncology Reports, 47, 97. https://doi.org/10.3892/or.2022.8308
MLA
Yu, X., Zhu, D., Luo, B., Kou, W., Cheng, Y., Zhu, Y."IFNγ enhances ferroptosis by increasing JAK‑STAT pathway activation to suppress SLCA711 expression in adrenocortical carcinoma". Oncology Reports 47.5 (2022): 97.
Chicago
Yu, X., Zhu, D., Luo, B., Kou, W., Cheng, Y., Zhu, Y."IFNγ enhances ferroptosis by increasing JAK‑STAT pathway activation to suppress SLCA711 expression in adrenocortical carcinoma". Oncology Reports 47, no. 5 (2022): 97. https://doi.org/10.3892/or.2022.8308
Copy and paste a formatted citation
x
Spandidos Publications style
Yu X, Zhu D, Luo B, Kou W, Cheng Y and Zhu Y: IFNγ enhances ferroptosis by increasing JAK‑STAT pathway activation to suppress SLCA711 expression in adrenocortical carcinoma. Oncol Rep 47: 97, 2022.
APA
Yu, X., Zhu, D., Luo, B., Kou, W., Cheng, Y., & Zhu, Y. (2022). IFNγ enhances ferroptosis by increasing JAK‑STAT pathway activation to suppress SLCA711 expression in adrenocortical carcinoma. Oncology Reports, 47, 97. https://doi.org/10.3892/or.2022.8308
MLA
Yu, X., Zhu, D., Luo, B., Kou, W., Cheng, Y., Zhu, Y."IFNγ enhances ferroptosis by increasing JAK‑STAT pathway activation to suppress SLCA711 expression in adrenocortical carcinoma". Oncology Reports 47.5 (2022): 97.
Chicago
Yu, X., Zhu, D., Luo, B., Kou, W., Cheng, Y., Zhu, Y."IFNγ enhances ferroptosis by increasing JAK‑STAT pathway activation to suppress SLCA711 expression in adrenocortical carcinoma". Oncology Reports 47, no. 5 (2022): 97. https://doi.org/10.3892/or.2022.8308
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