ArticleJournal of cancer research and clinical oncology2014
A cisplatin-resistant head and neck cancer cell line with cytoplasmic p53(mut) exhibits ATP-binding cassette transporter upregulation and high glutathione levels.
Article in Journal of cancer research and clinical oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- A novel fumaric acid metabolism-related prognostic signature associated with prognosis and immune infiltration landscape in laryngeal squamous cell carcinoma.Translational cancer research · 2025Article
- WNT3 promotes chemoresistance to oxaliplatin in oral squamous cell carcinoma via regulating ABCG2 expression.Cell & bioscience · 2025Article
- The Possibility of Plasma Membrane Transporters as Drug Targets in Oral Cancers.International journal of molecular sciences · 2025Review
- Lipid-Coated Polymeric Nanoparticles for the Photodynamic Therapy of Head and Neck Squamous Cell Carcinomas.Pharmaceutics · 2023Article
- M2 tumor-associated macrophage mediates the maintenance of stemness to promote cisplatin resistance by secreting TGF-β1 in esophageal squamous cell carcinoma.Journal of translational medicine · 2023Article
- The importin beta superfamily member RanBP17 exhibits a role in cell proliferation and is associated with improved survival of patients with HPV+ HNSCC.BMC cancer · 2022Article
- Activation ofCancers · 2022Article
- GADD45α alleviates the CDDP resistance of SK-OV3/cddp cells via redox-mediated DNA damage.Oncology letters · 2021Article
- Increased ABCC2 expression predicts cisplatin resistance in non-small cell lung cancer.Cell biochemistry and function · 2021Article
- The Molecular Basis and Therapeutic Aspects of Cisplatin Resistance in Oral Squamous Cell Carcinoma.Frontiers in oncology · 2021Review
- Combined EGFR1 and PARP1 Inhibition Enhances the Effect of Radiation in Head and Neck Squamous Cell Carcinoma Models.Radiation research · 2020Article
- EGFR Blockade Reverses Cisplatin Resistance in Human Epithelial Ovarian Cancer Cells.Iranian biomedical journal · 2020Article
- Article
- The Microenvironment of Tongue Cancer.Advances in experimental medicine and biology · 2020Review
- A Novel Multimodal NIR-II Nanoprobe for the Detection of Metastatic Lymph Nodes and Targeting Chemo-Photothermal Therapy in Oral Squamous Cell Carcinoma.Theranostics · 2019Article
- p53 and metabolism: from mechanism to therapeutics.Oncotarget · 2018Review
- Mitochondrial dysfunction enhances cisplatin resistance in human gastric cancer cells via the ROS-activated GCN2-eIF2α-ATF4-xCT pathway.Oncotarget · 2016Article
- Kinetic Modeling of ABCG2 Transporter Heterogeneity: A Quantitative, Single-Cell Analysis of the Side Population Assay.PLoS computational biology · 2016Article
- Article
- Dynamic cellular and molecular modulations of diabetes mediated head and neck carcinogenesis.Oncotarget · 2015Article
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Authors and funding
19 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeHead and neck squamous cell carcinoma (HNSCC) cell lines with cytoplasmically sequestered mutant p53 (p53(mut_c)) are frequently more resistant to cisplatin (CDDP) than cells with mutant but nuclear p53 (p53(mut_n)). The aim of the study was to identify underlying mechanisms implicated in CDDP resistance of HNSCC cells carrying cytoplasmic p53(mut).
methodsMicroarray analysis, quantitative reverse transcription polymerase chain reaction, Western blot analysis and immunocytochemistry were used to identify and evaluate candidate genes involved in CDDP resistance of p53(mut_c) cells. RNAi knockdown or treatment with inhibitors together with flow cytometry-based methods was used for functional assessment of the identified candidate genes. Cellular metabolic activity was assessed with the XTT assay, and the redox capacity of cells was evaluated by measuring cellular glutathione (GSH) levels.
resultsUpregulation of ABCC2 and ABCG2 transporters was observed in CDDP-resistant p53(mut_c) HNSCC cells. Furthermore, p53(mut_c) cells exhibited a pronounced side population that could be suppressed by RNAi knockdown of ABCG2 as well as treatment with the ATP-binding-cassette transporter inhibitors imatinib, MK571 and tariquidar. Metabolic activity and cellular GSH levels were higher in CDDP-resistant p53(mut_c) cells, consistent with a higher capacity to fend off cytotoxic oxidative effects such as those caused by CDDP treatment. Finally, ABCC2/G2 inhibition of HNSCC cells with MK571 markedly enhanced CDDP sensitivity of HNSCC cells.
conclusionsThe observations in this study point to a major role of p53(mut_c) in conferring a stem cell like phenotype to HNSCC cells that is associated with ABCC2/G2 overexpression, high GSH and metabolic activity levels as well as CDDP resistance.
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