Evidence map›Paper›PMID 34473785›Full record

ArticlePloS one2021

Nrf2 signaling promotes cancer stemness, migration, and expression of ABC transporter genes in sorafenib-resistant hepatocellular carcinoma cells.

Luping Gao, Yuji Morine, Shinichiro Yamada, Yu Saito, Tetsuya Ikemoto, Kazunori Tokuda, Chie Takasu, Katsuki Miyazaki, Mitsuo Shimada

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.4field-weighted citation impact, top 10% 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

28 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
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  9. Targeted Drug Nanodelivery and Immunotherapy for Combating Tumor Resistance.Combinatorial chemistry & high throughput screening · 2025
    Review
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  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Review
  17. Natural medicinal compounds target signal transduction pathways to overcome ABC drug efflux transporter-mediated multidrug resistance in cancer.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2023
    Review
  18. [Research progress on the mechanism and response strategies of molecular targeted drug resistance in liver cancer].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2023
    Article
  19. Article
  20. 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

9 authors at 1 institution in 1 country.

Luping GaoDepartment of Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Yuji MorineDepartment of Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Shinichiro YamadaDepartment of Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Yu SaitoDepartment of Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Tetsuya IkemotoDepartment of Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Kazunori TokudaDepartment of Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Chie TakasuDepartment of Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Katsuki MiyazakiDepartment of Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Mitsuo ShimadaDepartment of Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Tokushima University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

aimAs a multiple tyrosine kinase inhibitor, sorafenib is widely used to treat hepatocellular carcinoma (HCC), but patients frequently face resistance problems. Because the mechanism controlling sorafenib-resistance is not well understood, this study focused on the connection between tumor characteristics and the Nrf2 signaling pathway in a sorafenib-resistant HCC cell line.

methodsA sorafenib-resistant HCC cell line (Huh7) was developed by increasing the dose of sorafenib in the culture medium until the target concentration was reached. Cell morphology, migration/invasion rates, and expression of stemness-related and ATP-binding cassette (ABC) transporter genes were compared between sorafenib-resistant Huh7 cells and parental Huh7 cells. Next, a small interfering RNA was used to knock down Nrf2 expression in sorafenib-resistant Huh7 cells, after which cell viability, stemness, migration, and ABC transporter gene expression were examined again.

resultsProliferation, migration, and invasion rates of sorafenib-resistant Huh7 cells were significantly increased relative to the parental cells with or without sorafenib added to the medium. The expression levels of stemness markers and ABC transporter genes were up-regulated in sorafenib-resistant cells. After Nrf2 was knocked down in sorafenib-resistant cells, cell migration and invasion rates were reduced, and expression levels of stemness markers and ABC transporter genes were reduced.

conclusionNrf2 signaling promotes cancer stemness, migration, and expression of ABC transporter genes in sorafenib-resistant HCC cells.

Indexed as

Gene ExpressionGene Expression Regulation, NeoplasticAntineoplastic AgentsATP-Binding Cassette TransportersCarcinoma, HepatocellularCell Line, TumorCell MovementCell ProliferationCell SurvivalDrug Resistance, NeoplasmGene Knockdown TechniquesHumansLiver NeoplasmsNF-E2-Related Factor 2Protein Kinase InhibitorsSignal TransductionAntineoplastic AgentsATP-Binding Cassette TransportersNFE2L2 protein, humanNF-E2-Related Factor 2Protein Kinase InhibitorsSorafenib

Identifiers

PMID34473785
PMCPMC8412368
OpenAlexW3198212834

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.