Evidence map›Paper›PMID 38926262›Full record

ArticleJournal of endocrinological investigation2025

Bromocriptine sensitivity in bromocriptine-induced drug-resistant prolactinomas is restored by inhibiting FGF19/FGFR4/PRL.

Z Zhu, B Hu, D Zhu, X Li, D Chen, N Wu, Q Rao, Z Zhang, H Wang, Y Zhu

Abstract read
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In one paragraph

Article in Journal of endocrinological investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

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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

1 citing paper in PubMed.

  1. Article
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.

Z Zhu *Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-Sen University, No.74 Zhongshan Road 2, Guangzhou, 510080, Guangdong, China.ORCID http://orcid.org/0000-0001-9088-5890
B Hu *Department of Neurosurgery and Pituitary Tumor Center, The First Affiliated Hospital, Sun Yat-Sen University, No.58 Zhongshan Road 2, Guangzhou, 510080, Guangdong, China.
D ZhuDepartment of Neurosurgery and Pituitary Tumor Center, The First Affiliated Hospital, Sun Yat-Sen University, No.58 Zhongshan Road 2, Guangzhou, 510080, Guangdong, China.
X LiDepartment of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-Sen University, No.74 Zhongshan Road 2, Guangzhou, 510080, Guangdong, China.
D ChenDepartment of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-Sen University, No.74 Zhongshan Road 2, Guangzhou, 510080, Guangdong, China.
N WuDepartment of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-Sen University, No.74 Zhongshan Road 2, Guangzhou, 510080, Guangdong, China.
Q RaoDepartment of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-Sen University, No.74 Zhongshan Road 2, Guangzhou, 510080, Guangdong, China.
Z ZhangDepartment of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-Sen University, No.74 Zhongshan Road 2, Guangzhou, 510080, Guangdong, China.
H WangDepartment of Neurosurgery and Pituitary Tumor Center, The First Affiliated Hospital, Sun Yat-Sen University, No.58 Zhongshan Road 2, Guangzhou, 510080, Guangdong, China. wanghaij@mail.sysu.edu.cn.
Y ZhuDepartment of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-Sen University, No.74 Zhongshan Road 2, Guangzhou, 510080, Guangdong, China. zhuyongh@mail.sysu.edu.cn.

Funding

Guangdong Provincial Department of Science and Technology 2020A1515010297Guangdong Provincial Department of Science and Technology 2022A1515011265Sun Yat-sen University 2016008
6 · The paper itself

Abstract

purposeAt present, various treatment strategies are available for pituitary adenomas, including medications, surgery and radiation. The guidelines indicate that pharmacological treatments, such as bromocriptine (BRC) and cabergoline (CAB), are important treatments for prolactinomas, but drug resistance is an urgent problem that needs to be addressed. Therefore, exploring the mechanism of drug resistance in prolactinomas is beneficial for clinical treatment.

methodsIn our research, BRC-induced drug-resistant cells were established. Previous RNA sequencing data and an online database were used for preliminary screening of resistance-related genes. Cell survival was determined by Cell Counting Kit-8 (CCK-8) assay, colony formation assays and flow cytometry. Quantitative real-time polymerase chain reaction (qRT‒PCR), western blotting, immunohistochemistry, immunofluorescence and Co-immunoprecipitation (Co-IP) were used to assess the molecular changes and regulation. The therapeutic efficacy of BRC and FGFR4 inhibitor fisogatinib (FISO) combination was evaluated in drug-resistant cells and xenograft tumors in nude mice.

resultsConsistent with the preliminary results of RNA sequencing and database screening, fibroblast growth factor 19 (FGF19) expression was elevated in drug-resistant cells and tumor samples. With FGF19 silencing, drug-resistant cells exhibited increased sensitivity to BRC and decreased intracellular phosphorylated fibroblast growth factor receptor 4 (FGFR4) levels. After confirming that FGF19 binds to FGFR4 in prolactinoma cells, we found that FGF19/FGFR4 regulated prolactin (PRL) synthesis through the ERK1/2 and JNK signaling pathways. Regarding the effect of targeting FGF19/FGFR4 on BRC efficacy, FISO and BRC synergistically inhibited the growth of tumor cells, promoted apoptosis and reduced PRL levels.

conclusionOverall, our study revealed FGF19/FGFR4 as a new mechanism involved in the drug resistance of prolactinomas, and combination therapy targeting the pathway could be helpful for the treatment of BRC-induced drug-resistant prolactinomas.

Indexed as

BromocriptineDrug Resistance, NeoplasmFibroblast Growth FactorsPituitary NeoplasmsProlactinProlactinomaReceptor, Fibroblast Growth Factor, Type 4AnimalsCell Line, TumorFemaleHumansMaleMiceMice, NudeXenograft Model Antitumor AssaysBromocriptineFGF19 protein, humanFGFR4 protein, humanFibroblast Growth FactorsProlactinReceptor, Fibroblast Growth Factor, Type 4BromocriptineDrug resistanceFGF19FGFR4 inhibitorProlactinoma

Identifiers

PMID38926262

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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.