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Role of GPX4 inhibition-mediated ferroptosis in the chemoresistance of ovarian cancer to Taxol in vitro

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Abstract

Background

Ovarian cancer remains a common gynecological tumor and the fifth leading cause of death worldwide. Taxol-based chemotherapy is a standard approach to the treatment of ovarian cancer. Glutathione peroxidase 4 (GPX4) is the key regulator of ferroptosis, which is an important form of cell death. Here, we investigate the effect of GPX4 inhibition-mediated ferroptosis on the sensitivity of ovarian cancer cells to Taxol.

Methods and results

A2780/PTX and OVCAR-3/PTX Taxol-resistant ovarian cancer cells were established, and stable GPX4 knockout cell lines were generated via lentivirus GPX4-sgRNA. The GPX4 expression level, the apoptosis rate and cell viability were analyzed. The levels of ferroptosis-related factor indicators such as malondialdehyde (MDA) and reactive oxygen species (ROS) were measured. The results showed that the GPX4 protein and mRNA levels were increased in the Taxol-resistant cells. Moreover, GPX4 knockout reduced cell viability and inhibited the colony formation rate. In addition, we found that GPX4 inhibition increased Taxol sensitivity by inducing ferroptosis.

Conclusions

In summary, our studies reveal that GPX4 inhibition promotes ferroptosis and increases the sensitivity of ovarian cancer cells to Taxol in vitro.

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Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by grants from Shenzhen Healthcare Research Project (NO. SZLY2017030), Sanming Project of Medicine in Shenzhen (No. SZSM201812075), Shenzhen Science and Technology Program (No. JCYJ20210324134413038) and the National Natural Science Foundation of China (No. 82103124).

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Author notes

  1. Qi Feng, Sheng Hao and Peng Fang contribute equally to this work.

Authors and Affiliations

  1. National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, P. R. China

    Qi Feng & Xiugui Sheng

  2. Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, P. R. China

    Qi Feng & Peng Zhang

  3. Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Marshall Laboratory of Biomedical Engineering, Department of Biochemistry and Molecular Biology, International Cancer Center, Shenzhen University Medical School, Shenzhen, 518055, China

    Sheng Hao

  4. Guangdong Second Provincial General Hospital, Shenzhen, Guangdong, P. R. China

    Peng Fang

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  1. Qi Feng
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Contributions

In the paper, Q.F. and H.S. for data curation, formal analysis, technical support, methodology and original draft; F.P. supplemented partly experimental data and data curation, during the process of revising this manuscript; P.Z. and X.S. for revisions and comments on the manuscript; X.S. and Q.F. for Funding acquisition. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Peng Zhang or Xiugui Sheng.

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Feng, Q., Hao, S., Fang, P. et al. Role of GPX4 inhibition-mediated ferroptosis in the chemoresistance of ovarian cancer to Taxol in vitro. Mol Biol Rep 50, 10189–10198 (2023). https://doi.org/10.1007/s11033-023-08856-w

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  • DOI: https://doi.org/10.1007/s11033-023-08856-w

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