ArticleCancer management and research2018
Metformin sensitizes hypoxia-induced gefitinib treatment resistance of HNSCC via cell cycle regulation and EMT reversal.
Article in Cancer management and research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Hypoxia, metastatic origin and HPV16 E6/E7 expression differentially shape the radiation response in head and neck squamous cell carcinoma cell lines.Scientific reports · 2026Article
- Hypoxic Reprogramming of ACOX1-Driven HSP90AB1 Crotonylation Stabilizes Thioredoxin to Orchestrate Redox Homeostasis in Oral Squamous Cell Carcinoma.Research (Washington, D.C.) · 2026Article
- Understanding the Tumor Microenvironment and Therapy Resistance in Head and Neck Squamous Cell Carcinoma.Cells · 2025Review
- Protein crotonylation in cancer: mechanisms, functions, and therapeutic potential.Cell biology and toxicology · 2025Review
- Biological Anti-Tumoral Mechanisms of Metformin in Head and Neck Squamous Cell Carcinomas: A Systematic Review.Journal of clinical medicine · 2025Review
- Modulation of the Antitumor Response to Metformin, Caffeine, and Sodium Dichloroacetate by the Hypoxic Microenvironment in Lung Cancer Cells.International journal of molecular sciences · 2025Article
- Review
- Decreased expression of H19/miR-675 ameliorates hypoxia-induced oxaliplatin resistance in colorectal cancer.Heliyon · 2024Article
- The mechanisms of action of metformin on head and neck cancer in the pre-clinical setting: a scoping review.Frontiers in oncology · 2024Article
- Large-Scale Identification of Lysine Crotonylation Reveals Its Potential Role in Oral Squamous Cell Carcinoma.Cancer management and research · 2023Article
- Construction of a combined hypoxia and EMT index for head and neck squamous cell carcinoma.Frontiers in cell and developmental biology · 2022Article
- BST2 promotes growth and induces gefitinib resistance in oral squamous cell carcinoma via regulating the EGFR pathway.Archives of medical science : AMS · 2021Article
- Cancer stem cell secretome in the tumor microenvironment: a key point for an effective personalized cancer treatment.Journal of hematology & oncology · 2020Review
- Targeting Hypoxia Sensitizes TNBC to Cisplatin and Promotes Inhibition of Both Bulk and Cancer Stem Cells.International journal of molecular sciences · 2020Article
- Novel regulation of miR-34a-5p and HOTAIR by the combination of berberine and gefitinib leading to inhibition of EMT in human lung cancer.Journal of cellular and molecular medicine · 2020Article
- Metformin Combined with 4SC-202 Inhibited the Migration and Invasion of OSCC via STAT3/TWIST1.OncoTargets and therapy · 2020Article
- Metformin enhances gefitinib efficacy by interfering with interactions between tumor-associated macrophages and head and neck squamous cell carcinoma cells.Cellular oncology (Dordrecht, Netherlands) · 2019Article
- Metformin and 4SC-202 synergistically promote intrinsic cell apoptosis by accelerating ΔNp63 ubiquitination and degradation in oral squamous cell carcinoma.Cancer medicine · 2019Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesThe objectives of this study were to explore the mechanisms of metformin sensitization to hypoxia-induced gefitinib treatment in resistant head and neck squamous cell carcinoma (HNSCC) and evaluate the effects of this combined treatment strategy.
methodsThe effects of gefitinib treatment on HNSCC were measured under normoxic and hypoxic conditions. The relationship between hypoxia and cell cycle and epithelial-mesenchymal transition (EMT) in tumor cells were analyzed. Palbociclib and LY294002 were used in combination with gefitinib to evaluate the effects on HNSCC cell cytotoxicity during hypoxia. Finally, metformin was used to evaluate the sensitizing effects of gefitinib treatment on HNSCC in vivo and in vitro.
resultsCell viability and apoptosis assays demonstrated a significant difference in HNSCC cells treated with gefitinib between the normoxia and hypoxia groups. Hypoxia induced the expression of cyclin D1, decreased the percentage of cells in G1, and promoted the EMT of tumor cells. Both palbociclib and LY294002 enhanced gefitinib-induced cytotoxicity of HNSCC cells under hypoxic conditions. Encouragingly, metformin sensitized HNSCC to gefitinib treatment in vivo and in vitro.
conclusionHypoxia promotes G1-S cell cycle progression and EMT in HNSCC, resulting in gefitinib treatment resistance. Metformin sensitizes HNSCC to gefitinib treatment, which might serve as a novel combined treatment strategy.
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