Evidence map›Paper›PMID 33061451›Full record

ArticleOncoTargets and therapy2020

IL-6/STAT3 Signaling Contributes to Sorafenib Resistance in Hepatocellular Carcinoma Through Targeting Cancer Stem Cells.

Yu Li, Gang Chen, Zhijian Han, Huijuan Cheng, Liang Qiao, Yumin Li

RetractedErratum issuedOpen access · goldAbstract readRetracted Publication
PubMed Full text at PMC Publisher
In one paragraph

Article in OncoTargets and therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.1field-weighted citation impact, top 6% 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, 46 citations in OpenAlex.

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  9. EMT and Inflammation: Crossroads in HCC.Journal of gastrointestinal cancer · 2023
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  13. Cancer-Associated Fibroblasts in Hepatocellular Carcinoma and Cholangiocarcinoma.Cellular and molecular gastroenterology and hepatology · 2023
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 2 countries.

Yu LiGeneral Surgery Department, Lanzhou University Second Hospital, Lanzhou, Gansu, People's Republic of China.
Gang ChenGeneral Surgery Department, Lanzhou University Second Hospital, Lanzhou, Gansu, People's Republic of China.
Zhijian HanKey Laboratory of Digestive System Tumors of Gansu Province, Lanzhou University Second Hospital, Lanzhou, Gansu, People's Republic of China.
Huijuan ChengKey Laboratory of Digestive System Tumors of Gansu Province, Lanzhou University Second Hospital, Lanzhou, Gansu, People's Republic of China.
Liang QiaoStorr Liver Unit at the Westmead Millennium Institute, The University of Sydney at Westmead Hospital, Sydney, NSW 2145, Australia.ORCID 0000-0002-4723-8935
Yumin LiGeneral Surgery Department, Lanzhou University Second Hospital, Lanzhou, Gansu, People's Republic of China.ORCID 0000-0002-9267-1412
Gansu Provincial Hospital · CNLanzhou University Second Hospital · CNThe University of Sydney · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSorafenib is the standard first-line treatment for advanced hepatocellular carcinoma (HCC), even though acquired resistance to sorafenib has been found in many HCC patients, resulting in poor prognosis. Accumulating evidence demonstrates that liver cancer stem cells (LCSCs) contribute to sorafenib resistance in HCC. The inflammatory factor interleukin 6 (IL-6) plays a role in sorafenib resistance in HCC. However, the mechanism by which IL-6 in LCSCs is involved in the process of HCC sorafenib resistance remains elusive.

methodsIn this study, the sorafenib-resistant cell line PLC/PRF/5-R was generated by the concentration gradient method, and cell viability was determined by the CCK-8 assay. LCSCs were isolated from the PLC/PRF/5-R cell line by flow cytometry, and tumorigenesis was confirmed in nude mice. Blockade of IL-6 cells was achieved by lentiviral-mediated interference. The protein levels of stem cell markers (EpCAM, CD44), stemness markers (Oct3/4, β-catenin), and hepatocyte differentiation markers (glucose-6-phosphate, AFP) were measured by Western blotting analysis. Finally, a xenograft model was used to evaluate the function of IL-6 in the sorafenib resistance of HCC.

resultsThe stable sorafenib-resistant HCC cell line PLC/PRF/5-R was established and showed significant epithelial-mesenchymal transition (EMT) characteristics; the isolated resistant LCSCs from PLC/PRF/5-R were more tumorigenic than the control LCSCs. We showed that IL-6, IL-6R, STAT3 and GP130 expression were dramatically increased in resistant LCSCs compared to control LCSCs. Downregulation of IL-6 expression with short hairpin RNA (shRNA) restored sorafenib sensitivity in resistant LCSCs, suggesting the critical roles of IL-6/STAT3 in inducing sorafenib resistance. Furthermore, a xenograft tumor model showed that IL-6 downregulation improved the antitumor effect of sorafenib.

conclusionLCSCs play an important role in sorafenib-resistant HCC, and inhibition of the IL-6/STAT3 signaling pathway improves the antitumor effects of sorafenib against HCC in vitro and in vivo. These findings demonstrate that IL-6 in LCSCs may function as a novel target for combating sorafenib resistance in HCC.

Indexed as

cancer stem cellsdrug resistancehepatocellular carcinomaIL-6/STAT3 signalingsorafenib

Identifiers

PMID33061451
PMCPMC7533247
OpenAlexW3089376583

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.