Evidence map›Paper›PMID 35517821›Full record

ArticleFrontiers in pharmacology2022

Antitumor Effect of Simvastatin in Combination With DNA Methyltransferase Inhibitor on Gastric Cancer

Ying Xia, Yong Jin, Daxiang Cui, Xia Wu, Cunfeng Song, Weilin Jin, Hai Huang

Open access · goldAbstract read
In one paragraph

Article in Frontiers in pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
4.3field-weighted citation impact, top 4% of its field
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

31 citing papers in PubMed, 51 citations in OpenAlex.

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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

7 authors at 5 institutions in 1 country.

Ying XiaCenter for Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
Yong JinCenter for Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
Daxiang CuiShanghai Engineering Research Center for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Institute of Nano Biomedicine and Engineering, Shanghai Jiao Tong University, Shanghai, China.
Xia WuGuizhou Provincial People's Hospital, Guiyang, China.
Cunfeng SongShanghai Engineering Research Center for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Institute of Nano Biomedicine and Engineering, Shanghai Jiao Tong University, Shanghai, China.
Weilin JinShanghai Engineering Research Center for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Institute of Nano Biomedicine and Engineering, Shanghai Jiao Tong University, Shanghai, China.
Hai HuangCenter for Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
Affiliated Hospital of Guizhou Medical University · CNShanghai Jiao Tong University · CNFirst Hospital of Lanzhou University · CNGuiyang Medical University · CNGuizhou Provincial People's Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Gasdermin E (GSDME) is one of the executors of pyroptosis, a type of programmed lytic cell death, which can be triggered by caspase-3 activation upon stimulation. Silenced GSDME expression due to promoter hypermethylation is associated with gastric cancer (GC), which is confirmed in the present study by bioinformatics analysis and methylation-specific PCR (MSP) test of GC cell lines and clinical samples. GC cell lines and mouse xenograft models were used to investigate the pyroptosis-inducing effect of the common cholesterol-depleting, drug simvastatin (SIM), allied with upregulating GSDME expression by doxycycline (DOX)- inducible Tet-on system or DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine (5-Aza-CdR). Cell viability assessment and xenograft tumour growth demonstrated that the tumour inhibition effects of SIM can be enhanced by elevated GSDME expression. Morphological examinations and assays measuring lactate dehydrogenase (LDH) release and caspase-3/GSDME protein cleavage underlined the stimulation of pyroptosis as an important mechanism. Using short hairpin RNA (shRNA) knockdown of caspase-3 or GSDME, and caspase-3-specific inhibitors, we provided evidence of the requirement of caspase-3/GSDME in the pyroptosis process triggered by SIM. We conclude that reactivating GSDME expression and thereby inducing cancer cell-specific pyroptosis could be a potential therapeutic strategy against GC.

Indexed as

DNA methyltransferase inhibitorgastric cancerGSDMEpyroptosissimvastatin

Identifiers

PMID35517821
PMCPMC9065610
OpenAlexW4224291730

What Socratic holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.