Study on the Mechanism by Which GPX4 Expression Promotes Ferroptosis and Participates in Malignant Behavior of Endometrial Carcinoma

Xiaoxia DONG; Shuxian CHEN

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Xiaoxia DONG, Shuxian CHEN. Study on the Mechanism by Which GPX4 Expression Promotes Ferroptosis and Participates in Malignant Behavior of Endometrial Carcinoma[J]. Journal of Kunming Medical University.

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Xiaoxia DONG, Shuxian CHEN. Study on the Mechanism by Which GPX4 Expression Promotes Ferroptosis and Participates in Malignant Behavior of Endometrial Carcinoma[J]. Journal of Kunming Medical University.

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Study on the Mechanism by Which GPX4 Expression Promotes Ferroptosis and Participates in Malignant Behavior of Endometrial Carcinoma

Department of Gynecology，Shijiazhuang Maternal and Child Health Hospital，Shijiazhuang Hebei 050000，China

Received Date: 2025-07-30

Abstract

Abstract

Objective To investigate the mechanism by which Glutathione Peroxidase 4 （GPX4） expression promotes ferroptosis and participates in the malignant behavior of Endometrial Carcinoma （EC）. Methods The expression of GPX4 in EC tissues was determined by quantitative real-time PCR （qPCR）, Western blot, and immunohistochemistry （IHC）. KLE cells were cultured and divided into an shNC group （n = 6） and an shGPX4 group （n = 6）. The effects of GPX4 on EC cell proliferation, migration, and apoptosis were investigated using Transwell assay, colony formation assay, and flow cytometry. Intracellular Fe²⁺, reactive oxygen species （ROS）, and malondialdehyde （MDA） levels were detected. Mitochondrial membrane potential （MMP） was measured by JC-1 staining. GPX4 enzyme activity was assessed with a commercial kit. The content of lipid peroxide 4-hydroxynonenal （4-HNE） was determined by ELISA; and the expression of key ferroptosis-related proteins, Acyl-CoA Synthetase Long Chain Family Member 4 （ACSL4） and Solute Carrier Family 7 Member 11 （SLC7A11）, was analyzed by Western blot. A EC xenograft tumor model in nude mice was established and divided into an shNC group （n = 6） and an shGPX4 group （n = 6）. The in vivo effect of GPX4 knockdown was evaluated by measuring tumor volume, weight, and levels of Fe²⁺ and MDA. Results GPX4 was highly expressed in EC tissues and cell lines （GPX4 mRNA in EC tissues: 118.1±6.92 vs. 62.72±5.20 in adjacent normal tissues, t = 15.68, P < 0.001, Cohen’s d=8.62）.Compared with the shNC group, the shGPX4 group showed significantly decreased KLE cell proliferation （colony number: 0.37±0.05 vs. 0.89±0.07, t = 14.94, P < 0.001） and migration capacity, along with an increased apoptosis rate （61.64±7.03% vs. 12.60±2.48%, t = 16.12, P < 0.001）. Additionally, in the shGPX4 group, intracellular levels of Fe²⁺, lipid ROS, MDA, and 4-HNE were increased; GSH level and GPX4 enzyme activity were decreased; MMP was impaired; and the expression of ACSL4 was up-regulated while that of SLC7A11 was down-regulated （all P < 0.001）.In the nude mouse model, the shGPX4 group showed significantly reduced tumor volume （0.36±0.07 vs. 0.87±0.12 cm³, t = 9.07, P < 0.001） and weight, along with increased iron content and MDA levels in tumor tissues （both P < 0.001）. Conclusion The study demonstrates that GPX4 silencing can significantly induce ferroptosis, thereby reducing the proliferation and invasion of endometrial cancer cells, providing evidence for the study of potential treatment strategies for endometrial cancer.
- GPX4,
- ferroptosis,
- Endometrial cancer,
- Vicious behavior.

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References(15)

References

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