Evidence map›Paper›PMID 36401321›Full record

ArticleJournal of translational medicine2022

A novel small molecule glycolysis inhibitor WZ35 exerts anti-cancer effect via metabolic reprogramming.

Lihua Wang, Zheng Zhu, Qi Liang, Yecheng Tao, Gaowei Jin, Yaoyao Zhong, Jichen Dai, Ruixia Dai, Zhixiang Wang, Junbo Chen and 6 more

Open access · goldAbstract read
In one paragraph

Article in Journal of translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.9field-weighted citation impact, top 29% 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

6 citing papers in PubMed, 9 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

16 authors at 3 institutions in 1 country.

Lihua Wang *School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
Zheng Zhu *Department of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Qi Liang *Laboratory Animal Centre, Wenzhou Medical University, Wenzhou, 310020, Zhejiang, China.
Yecheng Tao *Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, 310000, Zhejiang, China.
Gaowei JinLaboratory Animal Centre, Wenzhou Medical University, Wenzhou, 310020, Zhejiang, China.
Yaoyao ZhongLaboratory Animal Centre, Wenzhou Medical University, Wenzhou, 310020, Zhejiang, China.
Jichen DaiLaboratory Animal Centre, Wenzhou Medical University, Wenzhou, 310020, Zhejiang, China.
Ruixia DaiLaboratory Animal Centre, Wenzhou Medical University, Wenzhou, 310020, Zhejiang, China.
Zhixiang WangLaboratory Animal Centre, Wenzhou Medical University, Wenzhou, 310020, Zhejiang, China.
Junbo ChenLaboratory Animal Centre, Wenzhou Medical University, Wenzhou, 310020, Zhejiang, China.
Lingjie ZhouLaboratory Animal Centre, Wenzhou Medical University, Wenzhou, 310020, Zhejiang, China.
Shouyu KeLaboratory Animal Centre, Wenzhou Medical University, Wenzhou, 310020, Zhejiang, China.
Bin ZhengLaboratory Animal Centre, Wenzhou Medical University, Wenzhou, 310020, Zhejiang, China.
Linhua LanKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
Xiaokun LinDepartment of Pediatric Surgery, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China. linxk2000@163.com.ORCID 0000-0001-6706-5309
Tongke ChenLaboratory Animal Centre, Wenzhou Medical University, Wenzhou, 310020, Zhejiang, China. dry136@wmu.edu.cn.
Wenzhou Medical University · CNShanghai Jiao Tong University · CNSir Run Run Shaw Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundLiver cancer is the fifth leading cause of cancer death worldwide, but early diagnosis and treatment of liver cancer remains a clinical challenge. How to screen and diagnose liver cancer early and prolong the survival rate is still the focus of researchers.

methodsCell experiments were used to detect the effect of WZ35 on the colony formation ability and proliferation activity of hepatoma cells, nude mouse experiment to observe the in vivo anticancer activity and toxic side effects of WZ35; metabolomics analysis, glucose metabolism experiment and Seahorse analysis of liver cancer cells treated with WZ35; cell experiments combined with bioinformatics analysis to explore the mechanism of WZ35-mediated metabolic reprogramming to exert anticancer activity; tissue microarray and case analysis to evaluate the clinical significance of biomarkers for early diagnosis, treatment and prognosis evaluation of liver cancer.

resultsWZ35 inhibited the proliferation activity of various cell lines of liver cancer, and showed good therapeutic effect in nude mice model of hepatocellular carcinoma without obvious toxic and side effects; WZ35 inhibited the absorption of glucose in hepatoma cells, and the drug effect glycolysis, phosphorylation and purine metabolism are relatively seriously damaged; WZ35 mainly inhibits YAP from entering the nucleus as a transcription factor activator by activating oxidative stress in liver cancer cells, reducing the transcription of GLUT1, and finally reducing its GLUT1. Tissue microarray and case analysis showed that GLUT1 and YAP were highly expressed and correlated in liver cancer patients, and were associated with poor patient prognosis. The GLUT1-YAP risk model had a high score in predicting prognosis.

conclusionThe study confirms that WZ35 is a small molecule glycolysis inhibitor, and through its properties, it mediates metabolic reprogramming dominated by impaired glycolysis, oxidative phosphorylation and purine metabolism to inhibit the proliferation activity of liver cancer cells. Our findings present novel insights into the pathology of liver cancer and potential targets for new therapeutic strategies. GLUT1-YAP has important reference significance for predicting the stages of disease progression in liver cancer patients and have the potential to serve as novel biomarkers for the diagnosis and treatment of liver cancer.

Indexed as

Carcinoma, HepatocellularLiver NeoplasmsAnimalsCell Line, TumorCurcuminGlucose Transporter Type 1GlycolysisMiceMice, NudePurinesReactive Oxygen SpeciesCurcuminGlucose Transporter Type 1PurinesReactive Oxygen SpeciesWZ35 compoundGLUT1Hepatocellular carcinomaMetabolic reprogrammingWZ35YAP

Identifiers

PMID36401321
PMCPMC9673307
OpenAlexW4309288099

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.