ArticleExperimental and therapeutic medicine2026
Metformin triggers apoptosis via endoplasmic reticulum stress in HER2-positive breast cancer cell lines.
Article in Experimental and therapeutic medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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.
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.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The antidiabetic drug metformin has potential as an anticancer agent, particularly due to its observed efficacy in breast cancer. Metformin exerts its cytotoxic effects in the induction of endoplasmic reticulum (ER) stress, which can trigger apoptotic cell death pathways. Therefore, the present study aimed to investigate the dose-dependent effects of metformin on ER stress and apoptosis in HER2-positive breast cancer SKBR3 cells. For this purpose, SKBR3 cells were treated with 5, 10 and 20 mM metformin. Cell proliferation was assessed using real-time cell analysis, while expression levels of ER stress-associated genes [glucose-regulated protein 78 kDa (GRP78), PRKR-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1), activating transcription factor 6 (ATF6) and CHOP)] were measured by revese transcription-quantitative PCR. Apoptosis was analyzed by Annexin V-FITC/PI flow cytometry in cells treated with 10 and 20 mM metformin. Findings revealed that metformin (5, 10 and 20 mM) dose-dependently inhibited cell proliferation and activated ER stress pathways. Significant increases were observed in gene expression following treatment with 5, 10 and 20 mM metformin, respectively, including GRP78 (3.70-, 5.06- and 7.33-fold; all P<0.0001) PERK (2.48-, 4.36- and 9.11-fold; all P<0.0001), IRE1 (2.15-fold, P=0.001; 2.90-fold, P<0.001; 5.55-fold, P<0.0001), ATF6 (2.43-2.44- and 3.63-fold; all P<0.0001) and particularly in pro-apoptotic CHOP (3.31-, 27.47- and 49.85-fold; all P<0.0001). Flow cytometry revealed that 10 and 20 mM metformin significantly increased early apoptosis to 6.05% (P<0.001) and 7.28% (P<0.001) and late apoptosis to 13.24% (P<0.001) and 20.59% (P<0.001), respectively, compared with controls (early apoptosis, 0.02%; late apoptosis, 0.05%). The present findings demonstrated that metformin activates ER stress response and induces apoptosis in HER2-positive breast cancer cells in a dose-dependent manner. This supports the potential of metformin as an adjuvant therapy, though further
Indexed as
Identifiers
What Socratic holds
Registered trials
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 Socratic graph.