Evidence map›Paper›PMID 40650854›Full record

ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2025

Resveratrol targets mitochondrial USP36-SOD2 to induce autophagy-ferroptosis and inhibit gastric cancer progression.

Xuan Zhao, Sheng Lu, Min Yan, Zheng-Gang Zhu, Feng Dong, Chao Yan

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Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
  2. Review
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  5. Mitochondrial Stress inAntioxidants (Basel, Switzerland) · 2026
    Review
  6. Article
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  8. Review
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

6 authors.

Xuan Zhao *Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, China.
Sheng Lu *Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, China.
Min YanDepartment of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, China.
Zheng-Gang ZhuDepartment of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, China.
Feng DongDepartment of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, China.
Chao YanDepartment of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, China. doctoryc@yeah.net.ORCID 0000-0002-3397-1992

Funding

Guangci Innovative Technology Launch Plan of Ruijin Hospital YW20220014Guangci Innovative Technology Launch Plan of Ruijin Hospital YW20240038
6 · The paper itself

Abstract

backgroundGastric cancer is an aggressive malignancy with high metastatic potential, limiting effective treatments. Resveratrol, a natural polyphenol, exhibits anti-cancer properties by modulating mitochondrial function and inducing programmed cell death (PCD) pathways. However, its role in mitochondrial disruption and the regulation of deubiquitination remains unclear.

methodsClinical samples and gastric cancer cell lines were analyzed to assess USP36 and SOD2 expression. Cells were treated with resveratrol, followed by functional assays (WB, qPCR, colony formation, Transwell migration, fluorescence staining) to evaluate its effects on USP36-mediated SOD2 stabilization, mitochondrial function, autophagy, and ferroptosis. A xenograft model was used to examine in vivo tumor growth.

resultsUSP36 deubiquitinates and stabilizes SOD2, thereby preserving mitochondrial integrity and facilitating tumor progression. Resveratrol disrupts this axis, reducing SOD2 stability, inducing mitochondrial dysfunction, and triggering autophagy and ferroptosis. In vitro, resveratrol significantly inhibited gastric cancer cell proliferation and migration; in vivo, it suppressed tumor growth.

conclusionThis study identifies the USP36-SOD2 axis as a critical driver of gastric cancer progression and reveals the therapeutic potential of resveratrol in targeting this pathway. By destabilizing mitochondrial function, resveratrol induces both autophagy and ferroptosis, thereby suppressing tumor progression and offering a promising strategy to improve clinical outcomes. Resveratrol inhibits USP36-mediated stabilization of SOD2, which further induces autophagy and ferroptosis by inducing mitochondrial damage and ROS accumulation, and suppressing tumor progression in a xenograft model. These findings underscore the USP36-SOD2 axis as a potential therapeutic target and highlight the adjunctive chemotherapeutic potential of resveratrol.

Indexed as

AutophagyFerroptosisMitochondriaResveratrolStomach NeoplasmsSuperoxide DismutaseUbiquitin ThiolesteraseAnimalsCell Line, TumorCell MovementCell ProliferationDisease ProgressionHumansMiceMice, NudeSuperoxide Dismutase 2ResveratrolSuperoxide DismutaseSuperoxide Dismutase 2Ubiquitin ThiolesteraseGastric cancerMitochondrial damageResveratrolSOD2USP36

Identifiers

PMID40650854

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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 OpenQuestion graph.