Evidence map›Paper›PMID 25576058›Full record

ArticleDiabetes2015

Metformin and Rapamycin Reduce Pancreatic Cancer Growth in Obese Prediabetic Mice by Distinct MicroRNA-Regulated Mechanisms.

Vincenza Cifarelli, Laura M Lashinger, Kaylyn L Devlin, Sarah M Dunlap, Jennifer Huang, Rudolf Kaaks, Michael N Pollak, Stephen D Hursting

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed, 4 pooled it
6.2field-weighted citation impact, top 3% 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

59 citing papers in PubMed, 4 syntheses or guidelines pooled it, 82 citations in OpenAlex.

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  19. Modeling pancreatic cancer in mice for experimental therapeutics.Biochimica et biophysica acta. Reviews on cancer · 2021
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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 5 institutions in 3 countries.

Vincenza CifarelliDepartment of Medicine, Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO.
Laura M LashingerDepartment of Nutritional Sciences, The University of Texas at Austin, Austin, TX.
Kaylyn L DevlinInstitute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX.
Sarah M DunlapDepartment of Nutritional Sciences, The University of Texas at Austin, Austin, TX.
Jennifer HuangDepartment of Nutritional Sciences, The University of Texas at Austin, Austin, TX.
Rudolf KaaksDivision of Epidemiology, German Cancer Research Center, Heidelberg, Germany.
Michael N PollakDepartments of Medicine and Oncology, McGill University, Montreal, Canada.
Stephen D HurstingDepartment of Nutritional Sciences, The University of Texas at Austin, Austin, TX Department of Nutrition, University of North Carolina, Chapel Hill, NC Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC hursting@email.unc.edu.
The University of Texas at Austin · USGerman Cancer Research Center · DEMcGill University · CAUniversity of North Carolina at Chapel Hill · USWashington University in St. Louis · US

Funding

Obesity and Pancreatic Cancer: The Role of IGF-1R01CA135386 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI FISCHER, SUSAN M · 2009 to 2012
$1.3M
NCI NIH HHS R01 CA135386NCI NIH HHS R01-CA-135386
6 · The paper itself

Abstract

Metformin treatment is associated with a decreased risk and better prognosis of pancreatic cancer (PC) in patients with type 2 diabetes, but the mechanism of metformin's PC growth inhibition in the context of a prediabetic state is unknown. We used a Panc02 pancreatic tumor cell transplant model in diet-induced obese (DIO) C57BL/6 mice to compare the effects of metformin and the direct mammalian target of rapamycin (mTOR) inhibitor rapamycin on PC growth, glucose regulation, mTOR pathway signaling, and candidate microRNA (miR) expression. In DIO/prediabetic mice, metformin and rapamycin significantly reduced pancreatic tumor growth and mTOR-related signaling. The rapamycin effects centered on decreased mTOR-regulated growth and survival signaling, including increased expression of let-7b and cell cycle-regulating miRs. Metformin (but not rapamycin) reduced glucose and insulin levels and expression of miR-34a and its direct targets Notch, Slug, and Snail. Metformin also reduced the number and size of Panc02 tumor spheres in vitro and inhibited the expression of Notch in spheroids. Our results suggest that metformin and rapamycin can both inhibit pancreatic tumor growth in obese, prediabetic mice through shared and distinct mechanisms. Metformin and direct mTOR inhibitors, alone or possibly in combination, represent promising intervention strategies for breaking the diabetes-PC link.

Indexed as

AnimalsBody WeightCell CycleDiet, DiabeticEnergy IntakeGlucose IntoleranceHypoglycemic AgentsImmunosuppressive AgentsMaleMetforminMiceMice, Inbred C57BLMice, ObeseMicroRNAsNeoplasms, ExperimentalPancreatic NeoplasmsHypoglycemic AgentsImmunosuppressive AgentsMetforminMicroRNAsSirolimusSNAI1 protein, humanSnai2 protein, mouseSnail Family Transcription FactorsTranscription FactorsVimentin

Identifiers

PMID25576058
PMCPMC4407853
OpenAlexW1965673106

What OpenQuestion holds

Texttitle and abstract
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.