ArticleOncotarget2017
Vorinostat and metformin sensitize EGFR-TKI resistant NSCLC cells via BIM-dependent apoptosis induction.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Prognostic and therapeutic importance of TROP-2 and MUC-1 in non-small cell lung cancer: A systematic review and meta-analysis.Biomedical reports · 2026Article
- Metformin Suppresses Metastatic Potential and Sensitizes Ovarian Cancer Cells to Chemotherapeutics.International journal of molecular sciences · 2026Article
- The antitumor effect of the novel agent MCL/ACT001 in pancreatic ductal adenocarcinoma.Journal of cancer research and clinical oncology · 2023Article
- The development and benefits of metformin in various diseases.Frontiers of medicine · 2023Review
- Article
- Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective.Signal transduction and targeted therapy · 2022Review
- Will We Unlock the Benefit of Metformin for Patients with Lung Cancer? Lessons from Current Evidence and New Hypotheses.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Vorinostat in autophagic cell death: A critical insight into autophagy-mediated, -associated and -dependent cell death for cancer prevention.Drug discovery today · 2022Review
- Hexokinases II-mediated glycolysis governs susceptibility to crizotinib in ALK-positive non-small cell lung cancer.Thoracic cancer · 2021Article
- [Research Progress of Epigenetic Mechanism in Acquired Resistance of Targeted Therapy in Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2021Review
- Molecular mechanisms underlining the role of metformin as a therapeutic agent in lung cancer.Cellular oncology (Dordrecht, Netherlands) · 2021Review
- Aspirin sensitizes osimertinib-resistant NSCLC cells in vitro and in vivo via Bim-dependent apoptosis induction.Molecular oncology · 2020Article
- Metformin Augments Panobinostat's Anti-Bladder Cancer Activity by Activating AMP-Activated Protein Kinase.Translational oncology · 2019Article
- Novel application of metformin combined with targeted drugs on anticancer treatment.Cancer science · 2019Review
- Pleiotropic Effects of Metformin on Cancer.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is a close relationship between low expression of BIM and resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). Vorinostat is a pan-histone deacetylase inhibitor (HDACi) that augments BIM expression in various types of tumor cells, however, this effect is attenuated by the high expression of anti-apoptotic proteins in EGFR-TKI resistant non-small cell lung cancer (NSCLC) cells. Vorinostat in combination with metformin - a compound that can inhibit anti-apoptotic proteins expression, might cooperate to activate apoptotic signaling and overcome EGFR-TKI resistance. This study aimed to investigate the cooperative effect and evaluate possible molecular mechanisms. The results showed that vorinostat combined with gefitinib augmented BIM expression and increased the sensitivity of EGFR-TKI resistant NSCLC cells to gefitinib, adding metformin simultaneously could obviously inhibit the expression of anti-apoptotic proteins, and further increased expression levels of BIM and BAX, and as a result, further improved the sensitivity of gefitinib both on the NSCLC cells with intrinsic and acquired resistance to EGFR-TKI. In addition, autophagy induced by gefitinib and vorinostat could be significantly suppressed by metformin, which might also contribute to enhance apoptosis and improve sensitivity of gefitinib. These results suggested that the combination of vorinostat and metformin might represent a novel strategy to overcome EGFR-TKI resistance associated with BIM-dependent apoptosis in larger heterogeneous populations.
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