Open Access

Expression of Ferredoxin1 in cisplatin‑resistant ovarian cancer cells confers their resistance against ferroptosis induced by cisplatin

  • Authors:
    • Ryosuke Takahashi
    • Koki Kamizaki
    • Keitaro Yamanaka
    • Yoshito Terai
    • Yasuhiro Minami
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  • Published online on: May 5, 2023     https://doi.org/10.3892/or.2023.8561
  • Article Number: 124
  • Copyright: © Takahashi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ovarian cancer (OC) is a refractory cancer that shows recurrence due to the acquisition of resistance to anticancer drugs, including cisplatin. However, the molecular mechanism underlying the acquisition of cisplatin resistance by cancer cells remains largely unknown. In the present study, two sets of ovarian endometrioid carcinoma cell lines were used: The parental A2780 cell line, the OVK18 cell line, and their derived cisplatin‑resistant cells. It was found that cisplatin could induce ferroptosis in these parental cells by enhancing mitochondrial membrane potential and lipid peroxidation as assessed by flow cytometric analysis, and that expression of Ferredoxin1 (Fdx1), an iron‑sulfur protein localized to the mitochondria, could be upregulated in cisplatin‑resistant cells in the absence of cisplatin. Intriguingly, it was shown that the siRNA‑mediated depletion of Fdx1 in cisplatin‑resistant cells resulted in enhanced ferroptosis by increasing the mitochondrial membrane potential and lipid peroxidation induced by cisplatin. By examining Fdx1 expression with immunohistochemical analysis in clinical specimens from patients with OC, higher expression of Fdx1 was detected in cisplatin‑resistant specimens than in cisplatin‑sensitive specimens. Collectively, these results indicated that Fdx1 may be a novel and suitable diagnostic/prognostic marker and therapeutic molecular target for the treatment of cisplatin‑resistant OC.
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June-2023
Volume 49 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Takahashi R, Kamizaki K, Yamanaka K, Terai Y and Minami Y: Expression of Ferredoxin1 in cisplatin‑resistant ovarian cancer cells confers their resistance against ferroptosis induced by cisplatin. Oncol Rep 49: 124, 2023
APA
Takahashi, R., Kamizaki, K., Yamanaka, K., Terai, Y., & Minami, Y. (2023). Expression of Ferredoxin1 in cisplatin‑resistant ovarian cancer cells confers their resistance against ferroptosis induced by cisplatin. Oncology Reports, 49, 124. https://doi.org/10.3892/or.2023.8561
MLA
Takahashi, R., Kamizaki, K., Yamanaka, K., Terai, Y., Minami, Y."Expression of Ferredoxin1 in cisplatin‑resistant ovarian cancer cells confers their resistance against ferroptosis induced by cisplatin". Oncology Reports 49.6 (2023): 124.
Chicago
Takahashi, R., Kamizaki, K., Yamanaka, K., Terai, Y., Minami, Y."Expression of Ferredoxin1 in cisplatin‑resistant ovarian cancer cells confers their resistance against ferroptosis induced by cisplatin". Oncology Reports 49, no. 6 (2023): 124. https://doi.org/10.3892/or.2023.8561