Evidence map›Paper›PMID 33922395›Full record

ArticleCancers2021

Ellagic Acid Resensitizes Gemcitabine-Resistant Bladder Cancer Cells by Inhibiting Epithelial-Mesenchymal Transition and Gemcitabine Transporters.

Ying-Si Wu, Jar-Yi Ho, Cheng-Ping Yu, Chun-Jung Cho, Chia-Lun Wu, Cheng-Shuo Huang, Hong-Wei Gao, Dah-Shyong Yu

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.4field-weighted citation impact, top 21% 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

13 citing papers in PubMed, 16 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

8 authors at 2 institutions in 1 country.

Ying-Si WuGraduate Institute of Pathology and Parasitology, National Defense Medical Center, Taipei 114, Taiwan.
Jar-Yi HoGraduate Institute of Pathology and Parasitology, National Defense Medical Center, Taipei 114, Taiwan.ORCID 0000-0001-6933-041X
Cheng-Ping YuGraduate Institute of Pathology and Parasitology, National Defense Medical Center, Taipei 114, Taiwan.ORCID 0000-0002-0693-5056
Chun-Jung ChoGraduate Institute of Pathology and Parasitology, National Defense Medical Center, Taipei 114, Taiwan.
Chia-Lun WuGraduate Institute of Pathology and Parasitology, National Defense Medical Center, Taipei 114, Taiwan.
Cheng-Shuo HuangGraduate Institute of Pathology and Parasitology, National Defense Medical Center, Taipei 114, Taiwan.
Hong-Wei GaoGraduate Institute of Pathology and Parasitology, National Defense Medical Center, Taipei 114, Taiwan.
Dah-Shyong YuGraduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.
National Defense Medical Center · TWTri-Service General Hospital · TW

Funding

Cheng Hsin General Hospital Foundation CH-NDMC-108-24, CH-NDMC-109-06 and CH-NDMC-110-10Ministry of Science and Technology, Taiwan MOST 109-2320-B-016-007 and MOST109-2314-B-016-038National Defense Medical Center MAB-109-064, MND-MAB-110-044, MAB-108-033 and MND-MAB-110-021Tri-Service General Hospital TSGH-D-109093, TSGH-D-110097, TSGH-C108-060, TSGH-D-109066 and TSGH-D-110068
6 · The paper itself

Abstract

Gemcitabine (GCB) resistance is a major issue in bladder cancer chemoresistance, but its underlying mechanism has not been determined. Epithelial-mesenchymal transition (EMT) has been shown to be comprehensively involved in GCB resistance in several other cancer types, but the direct connection between EMT and GCB remains unclear. This study was designed to elucidate the mechanism of EMT-related GCB resistance in bladder cancer and identify a potential phytochemical to modulate drug sensitivity. The biological effects of ellagic acid (EA) or its combined effects with GCB were compared in GCB-resistant cells and the GCB-sensitive line in terms of cell viability, apoptosis, motility, and in vivo tumorigenicity. The molecular regulation of EMT-related GCB resistance was evaluated at both the mRNA and protein expression levels. Our results indicated that TGF-β/Smad induced the overactivation of EMT in GCB-resistant cells and reduced the expression of GCB influx transporters (hCNT1 and hENT1). Moreover, ellagic acid (EA) inhibited the TGF-β signaling pathway both in vitro and in vivo by reducing Smad2, Smad3, and Smad4 expression and thereby resensitized GCB sensitivity. In conclusion, our results demonstrate that TGF-β/Smad-induced EMT contributes to GCB resistance in bladder cancer by reducing GCB influx and also elucidate the novel mechanisms of EA-mediated inhibition of TGF-β/Smad-induced EMT to overcome GCB resistance. Our study warrants further investigation of EA as an effective therapeutic adjuvant agent for overcoming GCB resistance in bladder cancer.

Indexed as

bladder cancerellagic acidgemcitabine resistancehCNT1 and hENT1TGF-β/Smad signaling pathway

Identifiers

PMID33922395
PMCPMC8122772
OpenAlexW3153573254

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.