Evidence map›Paper›PMID 42350991›Full record

ArticleBMC cancer2026

Metformin inhibits small intestinal neuroendocrine tumor growth in vivo.

Fredrik Axling, Samuel Backman, Per Hellman, Olov Norlén, Elham Barazeghi, Peter Stålberg

Abstract read
In one paragraph

Article in BMC cancer, 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

6 authors.

Fredrik AxlingDepartment of Surgical Sciences, Rudbeck Laboratory, Uppsala University, Uppsala University Hospital, Uppsala, SE-751 85, Sweden. Fredrik.axling@uu.se.
Samuel BackmanDepartment of Surgical Sciences, Rudbeck Laboratory, Uppsala University, Uppsala University Hospital, Uppsala, SE-751 85, Sweden.
Per HellmanDepartment of Surgical Sciences, Rudbeck Laboratory, Uppsala University, Uppsala University Hospital, Uppsala, SE-751 85, Sweden.
Olov NorlénDepartment of Surgical Sciences, Rudbeck Laboratory, Uppsala University, Uppsala University Hospital, Uppsala, SE-751 85, Sweden.
Elham Barazeghi *Department of Surgical Sciences, Rudbeck Laboratory, Uppsala University, Uppsala University Hospital, Uppsala, SE-751 85, Sweden. elham.barazeghi@uu.se.ORCID http://orcid.org/0000-0003-2943-0613
Peter Stålberg *Department of Surgical Sciences, Rudbeck Laboratory, Uppsala University, Uppsala University Hospital, Uppsala, SE-751 85, Sweden.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSmall intestinal neuroendocrine tumors (SI-NETs) are slow-growing but highly metastatic, with most patients presenting metastases at diagnosis. Radical surgery remains the only potential curative option when feasible. Consequently, there is a critical need for novel therapeutic strategies that can limit tumor progression and enable more personalized treatment approaches in combination with current clinical practices. In this study, we evaluated the impact of metformin on SI-NET cell growth in vivo, characterized the associated microRNA expression profile, and identified potential driver genes modulated by metformin treatment.

methodsA total of 22 SI-NET xenograft mouse models were established using CNDT2.5 and GOT1 cells. Mice were treated with metformin (2.56 mg/mL in drinking water) or water as control for 4 weeks. To explore the molecular impact of metformin, both small-RNA and total-RNA sequencing were performed on the dissected xenograft tumors. Proliferation and apoptosis were further evaluated by immunohistochemistry.

resultsIn vivo treatment of SI-NET cells with metformin led to a reduction in tumor size in both CNDT2.5 and GOT1 xenograft models. Our sequencing analyses identified seven altered microRNAs and 1,776 differentially expressed genes in metformin-treated tumors compared to controls. To uncover potential driver genes in SI-NETs affected by metformin, we compared the differentially expressed genes from GOT1 xenograft model with those identified by comparing single-cell RNA profile of enterochromaffin cells to SI-NETs. This novel approach revealed a set of significantly regulated genes, including those involved in tumor proliferation, apoptosis, and metastasis, as well as genes related to voltage-gated calcium channels and signal transduction.

conclusionsOur novel findings support further investigation of metformin as a potential therapeutic agent in clinical trials for SI-NET patients, and suggest that identified miRNAs should be assessed as potential predictive biomarkers for metformin treatment. This study highlights novel candidate driver genes affected by metformin, which are associated with key cellular processes and enterochromaffin cell's function, offering insights into the underlying mechanisms in SI-NETs.

Indexed as

Intestinal NeoplasmsIntestine, SmallMetforminNeuroendocrine TumorsAnimalsApoptosisCell Line, TumorCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansMiceMicroRNAsXenograft Model Antitumor AssaysMetforminMicroRNAsmetforminmiRNA-seqNeuroendocrine tumorsRNA-seqSI-NETs

Identifiers

PMID42350991
PMCPMC13295228

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.