Evidence map›Paper›PMID 42403706›Full record

ArticleFrontiers in pharmacology2026

Morusin targeting GDF15 enhances ferroptosis and overcomes cisplatin resistance in NSCLC.

Liang Zhang, Huan Liu, Si Jiang, Desheng Li, Xin Li, Maolei Xu, Jianwen Fei, Ling Zhou

Abstract read
In one paragraph

Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Liang Zhang *Department of Respiratory and Critical Care Medicine, Yantaishan Hospital Affiliated to Binzhou Medical University, Binzhou Medical University, Yantai, Shandong, China.
Huan Liu *The Key Laboratory of Traditional Chinese Medicine Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine, School of Pharmacy, Binzhou Medical University, YanTai, Shandong, China.
Si JiangThe Key Laboratory of Traditional Chinese Medicine Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine, School of Pharmacy, Binzhou Medical University, YanTai, Shandong, China.
Desheng LiThe Key Laboratory of Traditional Chinese Medicine Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine, School of Pharmacy, Binzhou Medical University, YanTai, Shandong, China.
Xin LiThe Key Laboratory of Traditional Chinese Medicine Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine, School of Pharmacy, Binzhou Medical University, YanTai, Shandong, China.
Maolei XuThe Key Laboratory of Traditional Chinese Medicine Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine, School of Pharmacy, Binzhou Medical University, YanTai, Shandong, China.
Jianwen FeiDepartment of Respiratory and Critical Care Medicine, Yantaishan Hospital Affiliated to Binzhou Medical University, Binzhou Medical University, Yantai, Shandong, China.
Ling ZhouThe Key Laboratory of Traditional Chinese Medicine Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine, School of Pharmacy, Binzhou Medical University, YanTai, Shandong, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: The natural compound morusin (Mor) acts as a potent tumor suppressor in non-small cell lung cancer (NSCLC), but its potential to sensitize DDP and its direct targets are less understood. This work aims to investigate the DDP-sensitizing effects of Mor and the underlying mechanisms. Methods: Cell viability and drug synergy were assessed in NSCLC cells. Ferroptosis was evaluated by measuring lipid reactive oxygen species (ROS), iron accumulation, and the expression of ferroptosis markers. GDF15 was identified as a target via transcriptome sequencing. Its direct binding with Mor was confirmed by molecular docking. The ubiquitin-mediated degradation mechanism and its functional role in ferroptosis were validated using the proteasome inhibitor MG132, alongside GDF15 overexpression and knockdown models. Clinical relevance was assessed using TCGA database analysis. Results: Mor induces ferroptosis and significantly augments DDP sensitivity in both NSCLC and cisplatin-resistant A549 cells (A549/DDP). Mechanistically, Mor directly binds to GDF15 and promotes its ubiquitin-mediated degradation. Consequently, GDF15 overexpression reversed Mor-induced cytotoxicity and DDP sensitization. Furthermore, DDP exposure impairs intracellular GDF15 protein levels, and the Mor/DDP combination synergistically suppresses GDF15 in A549 cells. Notably, GDF15 expression is elevated in NSCLC cells compared to normal lung epithelial cells. However, A549/DDP cells exhibit diminished intracellular GDF15 protein relative to parental cells, while GDF15 transcription is upregulated. Knockdown of GDF15 augmented DDP sensitivity in resistant cells. Conclusion: Mor reverses DDP resistance by inducing GDF15 degradation and ferroptosis, suggesting that Mor-based combination therapy holds promise in treating NSCLC.

Indexed as

cisplatinferroptosisGDF15morusinNSCLC

Identifiers

PMID42403706
PMCPMC13328490

What Socratic holds

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Registered trials

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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 Socratic graph.