Evidence map›Paper›PMID 39511054›Full record

ArticleMedical oncology (Northwood, London, England)2024

ML385 promotes ferroptosis and radiotherapy sensitivity by inhibiting the NRF2-SLC7A11 pathway in esophageal squamous cell carcinoma.

Ling Yan, Huidong Hu, Lei Feng, Zhe Li, Chunyan Zheng, Junpeng Zhang, Xiaoyang Yin, Baosheng Li

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Medical oncology (Northwood, London, England), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed.

  1. Review
  2. Molecular subtyping-guided precision therapy for ESCC: biomarker-driven strategies and clinical translation pathways.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Ling YanClinical Medical College, Southwest Medical University, Luzhou, 646000, China.
Huidong HuClinical Medical College, Southwest Medical University, Luzhou, 646000, China.
Lei FengDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Shandong First Medical University, Jinan, 250117, China.
Zhe LiDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Shandong First Medical University, Jinan, 250117, China.
Chunyan ZhengDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Shandong First Medical University, Jinan, 250117, China.
Junpeng ZhangDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Shandong First Medical University, Jinan, 250117, China.
Xiaoyang YinDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Shandong First Medical University, Jinan, 250117, China.
Baosheng LiClinical Medical College, Southwest Medical University, Luzhou, 646000, China. bsli@sdfmu.edu.cn.

Funding

National Natural Science Foundation of China 81874224Natural Science Foundation of Shandong Province ZR2022ZD31Special Fund Project of the Central Government for Guiding Local Science and Technology Development of Shandong Province YDZX2022010
6 · The paper itself

Abstract

Radiotherapy is important in treating esophageal squamous cell carcinoma (ESCC) comprehensively. Resistance to radiotherapy is a prominent factor contributing to treatment failure in patients with ESCC. The objective of this study was to investigate the impact of ML385, an inhibitor of nuclear factor erythroid 2-related factor 2 (NRF2), on the radiosensitivity of ESCC and elucidate its underlying mechanism. We treated KYSE150 and KYSE510 cells with ML385 and ionising radiation separately or simultaneously, and observed the proliferation, apoptosis, cell cycle and ferroptosis of different conditions by colony formation assay and flow cytometry. Our findings reveal that NRF2 was activated by radiation and translocated from the cytoplasm to the nucleus after radiation. However, ML385 inhibited the expression and cytoplasm-to-nucleus translocation of NRF2. Compared with radiation, ML385 combined with radiation exhibited a significant inhibition on the clone formation ability of ESCC cells, induced apoptosis and promoted G2/M phase arrest. The treatment of ML385 combined with radiation markedly increased ROS and lipid peroxidation levels and decreased glutathione levels compared with the control, thus promoting the occurrence of ferroptosis. In addition, the expression trend of NRF2 was the same as that of proteins related ferroptosis, such as SLC7A11 and GPX4. After overexpression of SLC7A11, we found that significantly restored glutathione levels and alleviated ML385 combined with radiation-induced lipid peroxidation, indicating that ML385 plays a key role in radiotherapy sensitization by inhibiting the NRF2-SLC7A11 pathway. In vivo, ML385 also promoted the killing effect of radiation on xenografted tumours in nude mice. This study identifies NRF2 inhibitor ML385 as a radiosensitizer of ESCC, which highlights the therapeutic potential of the NRF2-SLC7A11 pathway and provides a deeper understanding of the mechanism of ferroptosis in esophageal squamous cell carcinoma.

Indexed as

Amino Acid Transport System y+Esophageal NeoplasmsEsophageal Squamous Cell CarcinomaFerroptosisMice, NudeNF-E2-Related Factor 2Radiation ToleranceAcetamidesAnimalsApoptosisBenzodioxolesCell Line, TumorCell ProliferationHumansMiceMice, Inbred BALB CAcetamidesAmino Acid Transport System y+BenzodioxolesML385NFE2L2 protein, humanNF-E2-Related Factor 2SLC7A11 protein, humanEsophageal squamous cell carcinomaFerroptosisML385NRF2Radiosensitivity

Identifiers

PMID39511054
PMCPMC11543766

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.