ArticleCancer science2018
Activation of AMPK by simvastatin inhibited breast tumor angiogenesis via impeding HIF-1α-induced pro-angiogenic factor.
Article in Cancer science, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Association Between Statin Use and Prognosis of Breast Cancer: A Meta-Analysis of Cohort Studies.Frontiers in oncology · 2020Pooled it
- Statin use and risk of contralateral breast cancer: an updated cohort study with landmark analysis.European journal of epidemiology · 2026Article
- Promotion of breast cancer by the DNPH1 enzyme.iScience · 2026Article
- Synergistic effects of sorafenib and cilostazol in HepG2 cells.Journal of biosciences · 2026Article
- Simvastatin-loaded liposomal nanoparticles as treatment for adenomyosis in a patient-derived xenograft mouse model: a pilot study.Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology · 2025Article
- Statin use and risk of breast cancer among women with benign breast disease: a Danish nationwide cohort study.British journal of cancer · 2025Article
- Immunohistochemical expression of parathyroid hormone-related protein and ezrin in invasive breast carcinoma of no special type: a retrospective analysis.Diagnostic pathology · 2025Article
- Repurposing of Metabolic Drugs Metformin and Simvastatin as an Emerging Class of Cancer Therapeutics.Pharmaceutical research · 2025Review
- The signature of extracellular vesicles in hypoxic breast cancer and their therapeutic engineering.Cell communication and signaling : CCS · 2024Review
- Article
- Review
- Shear Stress-Induced AMP-Activated Protein Kinase Modulation in Endothelial Cells: Its Role in Metabolic Adaptions and Cardiovascular Disease.International journal of molecular sciences · 2024Review
- Simvastatin Overcomes Resistance to Tyrosine Kinase Inhibitors in Patient-derived, Oncogene-driven Lung Adenocarcinoma Models.Molecular cancer therapeutics · 2024Article
- Molecular Imaging of Melanoma VEGF-expressing Tumors through [Anti-cancer agents in medicinal chemistry · 2024Article
- An In Vivo Dual-Observation Method to Monitor Tumor Mass and Tumor-Surface Blood Vessels for Developing Anti-Angiogenesis Agents against Submillimeter Tumors.International journal of molecular sciences · 2023Article
- Overcoming chemoresistance in non-angiogenic colorectal cancer by metformin via inhibiting endothelial apoptosis and vascular immaturity.Journal of pharmaceutical analysis · 2023Article
- Metformin and simvastatin synergistically suppress endothelin 1-induced hypoxia and angiogenesis in multiple cancer types.Cancer science · 2023Article
- New insights into the therapeutic potentials of statins in cancer.Frontiers in pharmacology · 2023Review
- Potential antitumour effect of all-trans retinoic acid on regorafenib-treated human colon cancer cell lines.Contemporary oncology (Poznan, Poland) · 2023Article
- KLF2 is a clinical diagnostic and treatment biomarker of breast cancer.Frontiers in cell and developmental biology · 2023Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Substantial data from preclinical studies have revealed the biphasic effects of statins on cardiovascular angiogenesis. Although some have reported the anti-angiogenic potential of statins in malignant tumors, the underlying mechanism remains poorly understood. The aim of this study is to elucidate the mechanism by which simvastatin, a member of the statin family, inhibits tumor angiogenesis. Simvastatin significantly suppressed tumor cell-conditioned medium-induced angiogenic promotion in vitro, and resulted in dose-dependent anti-angiogenesis in vivo. Further genetic silencing of hypoxia-inducible factor-1α (HIF-1α) reduced vascular endothelial growth factor and fibroblast growth factor-2 expressions in 4T1 cells and correspondingly ameliorated HUVEC proliferation facilitated by tumor cell-conditioned medium. Additionally, simvastatin induced angiogenic inhibition through a mechanism of post-transcriptional downregulation of HIF-1α by increasing the phosphorylation level of AMP kinase. These results were further validated by the fact that 5-aminoimidazole-4-carboxamide ribonucleotide reduced HIF-1α protein levels and ameliorated the angiogenic ability of endothelial cells in vitro and in vivo. Critically, inhibition of AMPK phosphorylation by compound C almost completely abrogated simvastatin-induced anti-angiogenesis, which was accompanied by the reduction of protein levels of HIF-1α and its downstream pro-angiogenic factors. These findings reveal the mechanism by which simvastatin induces tumor anti-angiogenesis, and therefore identifies the target that explains the beneficial effects of statins on malignant tumors.
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