Tier 3 — preclinical

SIRT6 restrains hyperactivated Nrf2 to enhance cisplatin response in lung cancer models

Zhengpan Xiao, Wanmeng Fu, Shuangshuang Wei, Yechun Pei, Yi Min, Dayong Wang
Biochemical and Biophysical Research Communications 2026 836:154563

Bibliography

PubMed
PMID 42727479
DOI
10.1016/j.bbrc.2026.154563

Study snapshot

DesignClinical database analysis plus genetic/pharmacological cell studies and mouse xenografts.
ModelA549 and HCC827 lung cancer cells and A549 xenografts.
SampleCell and xenograft experiments.
InterventionSIRT6 overexpression, MDL-800, Nrf2 manipulation and cisplatin.
DurationPreclinical treatment experiments.
EndpointsCisplatin sensitivity; Nrf2 transcriptional activity; Nrf2 acetylation/nuclear accumulation; Tumor growth

What the study showed, in plain terms

In lung-cancer models with excessive Nrf2 signaling, SIRT6 overexpression or MDL-800 improved cisplatin response. The work supports a tumor-suppressive/chemosensitizing SIRT6 role in this specific context.

Key findings

SIRT6 restrained hyperactivated Nrf2 signaling and enhanced cisplatin sensitivity in lung-cancer cells and xenografts, while the authors avoided claiming a fully defined direct deacetylation mechanism.

What this study can and cannot tell us

Preclinical; not a human treatment trial; cancer-context specific; does not justify self-directed SIRT6 activation during chemotherapy.

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Editorial review

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability