Evidence map›Paper›PMID 36978114›Full record

ArticleBMC pharmacology & toxicology2023

Thiram, an inhibitor of 11ß-hydroxysteroid dehydrogenase type 2, enhances the inhibitory effects of hydrocortisone in the treatment of osteosarcoma through Wnt/β-catenin pathway.

You Zhang, Nanjing Li, He Li, Maojia Chen, Wei Jiang, Wenhao Guo

Open access · goldFull text read
In one paragraph

Article in BMC pharmacology & toxicology, 2023. 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, top 94% 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

0 citing papers in PubMed, 0 citations in OpenAlex.

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

6 authors at 3 institutions in 1 country.

You Zhang *Clinical Translational Innovation Center/Molecular Medicine Research Center, West China Hospital, Sichuan Univicity, Chengdu, Sichuan Province, 610041, People's Republic of China.
Nanjing Li *Division of of Radiotherapy, Cancer Center,West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, People's Republic of China.
He LiWest China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan Province, 610044, People's Republic of China.
Maojia ChenAnimal Experiment Center, West China Hospital, Sichuan University, Chengdu, 610000, People's Republic of China.
Wei JiangClinical Translational Innovation Center/Molecular Medicine Research Center, West China Hospital, Sichuan Univicity, Chengdu, Sichuan Province, 610041, People's Republic of China. wenhaoguo2011@163.com.
Wenhao GuoDepartment of Abdominal Oncology, Cancer Center and State Key Laboratory of Biotherapy, Medical School, West China Hospital, Sichuan University, No. 37, Guoxue Road, Chengdu, Sichuan Province, 610041, People's Republic of China. wenhaoguo2011@163.com.
Sichuan University · CNWest China Hospital of Sichuan University · CNWest China Medical Center of Sichuan University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe anti-osteosarcoma effects of hydrocortisone and thiram, an inhibitor of type 2 11ß-hydroxysteroid dehydrogenase (11HSD2), have not been reported. The purpose of this study was to investigate the effects of hydrocortisone alone or the combination of hydrocortisone with thiram on osteosarcoma and the molecular mechanism, and determine whether they can be as new therapeutic agents for osteosarcoma.

methodsNormal bone cells and osteosarcoma cells were treated with hydrocortisone or thiram alone or in combination. The cell proliferation, migration, cell cycle and apoptosis were detected by using CCK8 assay, wound healing assay, and flow cytometry, respectively. An osteosarcoma mouse model was established. The effect of drugs on osteosarcoma in vivo was assessed by measuring tumor volume. Transcriptome sequencing, bioinformatics analysis, RT-qPCR, Western blotting (WB), enzymelinked immunosorbent assay (ELISA) and siRNA transfection were performed to determine the molecular mechanisms.

resultsHydrocortisone inhibited the proliferation and migration, and induced apoptosis and cell cycle arrest of osteosarcoma cells in vitro. Hydrocortisone also reduced the volume of osteosarcoma in mice in vivo. Mechanistically, hydrocortisone decreased the levels of Wnt/β-catenin pathway-associated proteins, and induced the expression of glucocorticoid receptor α (GCR), CCAAT enhancer-binding protein β (C/EBP-beta) and 11HSD2, resulting in a hydrocortisone resistance loop. Thiram inhibited the activity of the 11HSD2 enzyme, the combination of thiram and hydrocortisone further enhanced the inhibition of osteosarcoma through Wnt/β-catenin pathway.

conclusionsHydrocortisone inhibits osteosarcoma through the Wnt/β-catenin pathway. Thiram inhibits 11HSD2 enzyme activity, reducing hydrocortisone inactivation and promoting the effect of hydrocortisone through the same pathway.

Indexed as

Bone NeoplasmsOsteosarcoma11-beta-Hydroxysteroid Dehydrogenase Type 2AnimalsApoptosisbeta CateninCell Line, TumorCell ProliferationHydrocortisoneMiceThiramWnt Proteins11-beta-Hydroxysteroid Dehydrogenase Type 2beta CateninHSD11B2 protein, mouseHydrocortisoneThiramWnt Proteins11ß-hydroxysteroid dehydrogenase type 2HydrocortisoneOsteosarcomaThiramWnt/β-catenin pathway

Identifiers

PMID36978114
PMCPMC10045229
OpenAlexW4361223751

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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.