ArticleOncotarget2015
Metformin combined with aspirin significantly inhibit pancreatic cancer cell growth in vitro and in vivo by suppressing anti-apoptotic proteins Mcl-1 and Bcl-2.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.
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Who cites it
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- The relationship between the use of metformin and the risk of pancreatic cancer in patients with diabetes: a systematic review and meta-analysis.BMC gastroenterology · 2023 · on this mapPooled it
- Metformin as a Multifaceted Therapeutic Agent for Gastrointestinal Diseases: Mechanisms, Clinical Efficacy, and Future Directions.Pharmacology research & perspectives · 2026Review
- Metformin potentiates arsenic disulfide in diffuse large B-cell lymphoma: modulation of BAX/BCL-2 apoptotic pathway and hedgehog pathway.Frontiers in oncology · 2026Article
- Article
- Metformin and its Nanoformulations in Cancer Prevention and Therapy.Current pharmaceutical design · 2025Review
- Transformation of Ginsenosides byMolecules (Basel, Switzerland) · 2023Article
- Cyclooxygenase and Cancer: Fundamental Molecular Investigations.International journal of molecular sciences · 2023Article
- Metformin and Aspirin: Anticancer effects on A549 and PC3 cancer cells and the mechanisms of action.Toxicology research · 2023Article
- KRASJournal of cellular and molecular medicine · 2023Article
- Bioactive Ingredients inInternational journal of molecular sciences · 2023Article
- FNDC5 and AKR1B10 inhibit the proliferation and metastasis of adrenocortical carcinoma cells by regulating AMPK/mTOR pathway.Experimental and therapeutic medicine · 2023Article
- Aspirin increases the efficacy of gemcitabine in pancreatic cancer by modulating the PI3K/AKT/mTOR signaling pathway and reversing epithelial‑mesenchymal transition.Oncology letters · 2023Article
- Phosphoproteomic analysis of metformin signaling in colorectal cancer cells elucidates mechanism of action and potential therapeutic opportunities.Clinical and translational medicine · 2023Article
- The Role and Mechanism of Metformin in Inflammatory Diseases.Journal of inflammation research · 2023Review
- Metformin Treatment Modulates Long Non-Coding RNA Isoforms Expression in Human Cells.Non-coding RNA · 2022Article
- Effective combinations of anti-cancer and targeted drugs for pancreatic cancer treatment.World journal of gastroenterology · 2022Review
- Review
- Metformin improves renal injury of MRL/lpr lupus-prone mice via the AMPK/STAT3 pathway.Lupus science & medicine · 2022Article
- Dynamic switch of immunity and antitumor effects of metformin in rat spontaneous esophageal carcinogenesis.Cancer immunology, immunotherapy : CII · 2022Article
- Alisol B 23-Acetate Increases the Antitumor Effect of Bufalin on Liver Cancer through Inactivating Wnt/Computational and mathematical methods in medicine · 2022Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Metformin and aspirin have been studied extensively as cancer preventive or therapeutic agents. However, the effects of their combination on pancreatic cancer cells have not been investigated. Herein, we evaluated the effects of metformin and aspirin, alone or in combination, on cell viability, migration, and apoptosis as well as the molecular changes in mTOR, STAT3 and apoptotic signaling pathways in PANC-1 and BxPC3 cells. Metformin and aspirin, at relatively low concentrations, demonstrated synergistically inhibitory effects on cell viability. Compared to the untreated control or individual drug, the combination of metformin and aspirin significantly inhibited cell migration and colony formation of both PANC-1 and BxPC-3 cells. Metformin combined with aspirin significantly inhibited the phosphorylation of mTOR and STAT3, and induced apoptosis as measured by caspase-3 and PARP cleavage. Remarkably, metformin combined with aspirin significantly downregulated the anti-apoptotic proteins Mcl-1 and Bcl-2, and upregulated the pro-apoptotic proteins Bim and Puma, as well as interrupted their interactions. The downregulation of Mcl-1 and Bcl-2 was independent of AMPK or STAT3 pathway but partially through mTOR signaling and proteasome degradation. In a PANC-1 xenograft mouse model, we demonstrated that the combination of metformin and aspirin significantly inhibited tumor growth and downregulated the protein expression of Mcl-1 and Bcl-2 in tumors. Taken together, the combination of metformin and aspirin significantly inhibited pancreatic cancer cell growth in vitro and in vivo by regulating the pro- and anti-apoptotic Bcl-2 family members, supporting the continued investigation of this two drug combination as chemopreventive or chemotherapeutic agents for pancreatic cancer.
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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.