Evidence map›Paper›PMID 41898509›Full record

ArticleInternational journal of molecular sciences2026

LRRC8A Inhibition Overcomes Chemoresistance by Downregulating MRP3 and CYP3A4 in the 3D Spheroid Model of Human Breast Cancer Cells.

Ryo Otsuka, Junko Kajikuri, Miki Matsui, Hiroaki Kito, Ayano Kitahara, Hinako Mitsui, Yohei Yamaguchi, Tomoka Hisada, Tatsuya Toyama, Susumu Ohya

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of molecular sciences, 2026. 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
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.

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

10 authors.

Ryo OtsukaDepartment of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan.
Junko KajikuriDepartment of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan.ORCID 0000-0003-0598-0733
Miki MatsuiDepartment of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan.
Hiroaki KitoDepartment of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan.
Ayano KitaharaDepartment of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan.
Hinako MitsuiDepartment of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan.
Yohei YamaguchiDepartment of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan.ORCID 0000-0002-1947-0032
Tomoka HisadaDepartment of Breast Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan.
Tatsuya ToyamaDepartment of Breast Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan.
Susumu OhyaDepartment of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan.ORCID 0000-0002-5765-0667

Funding

Grant-in-Aid for Research in Nagoya City University 2312001Japan Society for the Promotion of Science JP20K07071Japan Society for the Promotion of Science JP24K09847Japan Society for the Promotion of Science JP24K10314Ministry of Education, Culture, Sports, Science and Technology JPMXS0441500024
6 · The paper itself

Abstract

Leucine-rich repeat-containing 8A (LRRC8A; also known as SWELL1), the essential subunit of volume-regulated anion channels (VRACs), is amplified in multiple malignancies and has been implicated in tumor progression and therapeutic resistance. Three-dimensional (3D) cancer spheroids have been well-established as in vitro models that recapitulate characteristics of tumor stemness and intrinsic drug resistance. In the present study, spheroid formation in human breast cancer cell lines, YMB-1 and MDA-MB-468, conferred resistance to multiple anticancer drugs, including doxorubicin (DOX), gemcitabine (GEM), and 5-fluorouracil (5-FU), thereby mimicking the characteristic properties of breast cancer stem-like cells. LRRC8A expression was upregulated in 3D spheroids compared with adherent 2D monolayers, and its pharmacological inhibition induced membrane hyperpolarization accompanied by intracellular Cl

Indexed as

ATP-Binding Cassette, Sub-Family C ProteinsBreast NeoplasmsCytochrome P-450 CYP3ADrug Resistance, NeoplasmMembrane ProteinsSpheroids, CellularAntineoplastic AgentsCell Line, TumorDown-RegulationDoxorubicinFemaleGene Expression Regulation, NeoplasticHumansAntineoplastic AgentsATP-Binding Cassette, Sub-Family C ProteinsCYP3A4 protein, humanCytochrome P-450 CYP3ADoxorubicinLRRC8A protein, humanMembrane Proteinsmultidrug resistance-associated protein 3breast cancercancer stemnesschemoresistanceCYP3A4LRRC8AMRP3NRF2

Identifiers

PMID41898509
PMCPMC13026703

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.