ArticleBritish journal of cancer2003
Increased sensitivity to gemcitabine of P-glycoprotein and multidrug resistance-associated protein-overexpressing human cancer cell lines.
Article in British journal of cancer, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
60 citing papers in PubMed, 166 citations in OpenAlex.
- CHOP versus GEM-P in previously untreated patients with peripheral T-cell lymphoma (CHEMO-T): a phase 2, multicentre, randomised, open-label trial.The Lancet. Haematology · 2018Trial
- Gemcitabine, cisplatin and methylprednisolone (GEM-P) is an effective salvage regimen in patients with relapsed and refractory lymphoma.British journal of cancer · 2005Trial
- Identification of Putative Equilibrative Nucleoside Transporter Inhibitors Through Dual-Pharmacophore Virtual Screening and Validation in a Gemcitabine-Based Cell Assay.Molecules (Basel, Switzerland) · 2026Article
- Review
- BH3 mimetic and dual PI3K/mTOR inhibitor attenuates gemcitabine resistance in triple-negative breast cancer.Medical oncology (Northwood, London, England) · 2025Article
- Exploring extracellular RNA as drivers of chemotherapy resistance in cancer.Molecular biology reports · 2025Review
- A BPTF Inhibitor That Interferes with the Multidrug Resistance Pump to Sensitize Murine Triple-Negative Breast Cancer Cells to Chemotherapy.International journal of molecular sciences · 2024Article
- Characterization of Chemoresistance in Pancreatic Cancer: A Look at MDR-1 Polymorphisms and Expression in Cancer Cells and Patients.International journal of molecular sciences · 2024Article
- Targeting ABC transporters in PDAC - past, present, or future?Oncotarget · 2024Article
- Fibroblast growth factor receptor 1 inhibition suppresses pancreatic cancer chemoresistance and chemotherapy-driven aggressiveness.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2024Article
- ABCB1 overexpression through locus amplification represents an actionable target to combat paclitaxel resistance in pancreatic cancer cells.Journal of experimental & clinical cancer research : CR · 2024Article
- Multidrug resistance protein 5 affects cell proliferation, migration and gemcitabine sensitivity in pancreatic cancer MIA Paca‑2 and PANC‑1 cells.Oncology reports · 2024Article
- Knockout cancer by nano-delivered immunotherapy using perfusion-aided scaffold-based tumor-on-a-chip.Nanotheranostics · 2024Review
- Targeting miRNA and using miRNA as potential therapeutic options to bypass resistance in pancreatic ductal adenocarcinoma.Cancer metastasis reviews · 2023Review
- Identification and Clinical Significance of Pancreatic Cancer Stem Cells and Their Chemotherapeutic Drug Resistance.International journal of molecular sciences · 2023Article
- Analysis of Multiple Drug Resistance Mechanism in Different Types of Soft Tissue Sarcomas: Assessment of the Expression of ABC-Transporters, MVP, YB-1, and Analysis of Their Correlation with Chemosensitivity of Cancer Cells.International journal of molecular sciences · 2022Article
- Nanomedicine Strategies for Management of Drug Resistance in Lung Cancer.International journal of molecular sciences · 2022Review
- Potential Role of Exosomes in the Chemoresistance to Gemcitabine and Nab-Paclitaxel in Pancreatic Cancer.Diagnostics (Basel, Switzerland) · 2022Review
- Preclinical models for development of immune-oncology therapies.Immuno-oncology insights · 2022Article
- Ursolic acid restores sensitivity to gemcitabine through the RAGE/NF-κB/MDR1 axis in pancreatic cancer cells and in a mouse xenograft model.Journal of food and drug analysis · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gemcitabine (2',2'-difluorodeoxycytidine) is a deoxycytidine analogue that is activated by deoxycytidine kinase (dCK) to its monophosphate and subsequently to its triphosphate dFdCTP, which is incorporated into both RNA and DNA, leading to DNA damage. Multidrug resistance (MDR) is characterised by an overexpression of the membrane efflux pumps P-glycoprotein (P-gP) or multidrug resistance-associated protein (MRP). Gemcitabine was tested against human melanoma, non-small-cell lung cancer, small-cell lung cancer, epidermoid carcinoma and ovarian cancer cells with an MDR phenotype as a result of selection by drug exposure or by transfection with the mdr1 gene. These cell lines were nine- to 72-fold more sensitive to gemcitabine than their parental cell lines. The doxorubicin-resistant cells 2R120 (MRP1) and 2R160 (P-gP) were nine- and 28-fold more sensitive to gemcitabine than their parental SW1573 cells, respectively (P<0.01), which was completely reverted by 25 micro M verapamil. In 2R120 and 2R160 cells, dCK activities were seven- and four-fold higher than in SW1573, respectively, which was associated with an increased dCK mRNA and dCK protein. Inactivation by deoxycytidine deaminase was 2.9- and 2.2-fold decreased in 2R120 and 2R160, respectively. dFdCTP accumulation was similar in SW1573 and its MDR variants after 24 h exposure to 0.1 micro M gemcitabine, but dFdCTP was retained longer in 2R120 (P<0.001) and 2R160 (P<0.003) cells. 2R120 and 2R160 cells also incorporated four- and six-fold more [(3)H]gemcitabine into DNA (P<0.05), respectively. P-glycoprotein and MRP1 overexpression possibly caused a cellular stress resulting in increased gemcitabine metabolism and sensitivity, while reversal of collateral gemcitabine sensitivity by verapamil also suggests a direct relation between the presence of membrane efflux pumps and gemcitabine sensitivity.
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