ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2014
Enhancement of 5-fluorouracil-induced cytotoxicity by leucovorin in 5-fluorouracil-resistant gastric cancer cells with upregulated expression of thymidylate synthase.
Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 42 citations in OpenAlex.
- PI3 expression predicts recurrence after chemotherapy with DNA-damaging drugs in gastric cancer.The Journal of pathology · 2025Article
- A novel approach for the co-delivery of 5-fluorouracil and everolimus for breast cancer combination therapy: stimuli-responsive chitosan hydrogel embedded with mesoporous silica nanoparticles.Journal of translational medicine · 2025Article
- Development of an all-in-one real-time PCR assay for simultaneous detection of spotted fever group rickettsiae, severe fever with thrombocytopenia syndrome virus and hantaan virus prevalent in central China.PLoS neglected tropical diseases · 2024Article
- Lineage of drug discovery research on fluorinated pyrimidines: chronicle of the achievements accomplished by Professor Setsuro Fujii.International journal of clinical oncology · 2023Article
- FOLFIRINOX Pharmacodynamic Interactions in 2D and 3D Pancreatic Cancer Cell Cultures.The AAPS journal · 2022Article
- MeCP2 confers 5-fluorouracil resistance in gastric cancer via upregulating the NOX4/PKM2 pathway.Cancer cell international · 2022Article
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- Expression of CD44v6-Containing Isoforms Influences Cisplatin Response in Gastric Cancer Cells.Cancers · 2020Article
- Study of Thymidylate Synthase (TS) and Dihydropyrimidine Dehydrogenase (DPD) Expressions on 5-Fluorouracil in Oral Squamous Cell CarcinomaAsian Pacific journal of cancer prevention : APJCP · 2019Article
- Increase of PRPP enhances chemosensitivity of PRPS1 mutant acute lymphoblastic leukemia cells to 5-Fluorouracil.Journal of cellular and molecular medicine · 2018Article
- Galactosylated Chitosan-Functionalized Mesoporous Silica Nanoparticle Loading by Calcium Leucovorin for Colon Cancer Cell-Targeted Drug Delivery.Molecules (Basel, Switzerland) · 2018Article
- Trifluridine/tipiracil overcomes the resistance of human gastric 5-fluorouracil-refractory cells with high thymidylate synthase expression.Oncotarget · 2018Article
- Article
- Epigenomics alternations and dynamic transcriptional changes in responses to 5-fluorouracil stimulation reveal mechanisms of acquired drug resistance of colorectal cancer cells.The pharmacogenomics journal · 2018Article
- Article
- Inhibition of PI3K suppresses propagation of drug-tolerant cancer cell subpopulations enriched by 5-fluorouracil.Scientific reports · 2017Article
- Gambogic acid potentiates the chemosensitivity of colorectal cancer cells to 5-fluorouracil by inhibiting proliferation and inducing apoptosis.Experimental and therapeutic medicine · 2017Article
- Targeting nuclear thymidylate biosynthesis.Molecular aspects of medicine · 2017Review
- Identifying clinically relevant drug resistance genes in drug-induced resistant cancer cell lines and post-chemotherapy tissues.Oncotarget · 2015Article
- TAS-102, a novel antitumor agent: a review of the mechanism of action.Cancer treatment reviews · 2015Review
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9 authors at 2 institutions in 1 country.
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Abstract
backgroundElucidation of the mechanisms by which gastric cancer cells acquire resistance to 5-fluorouracil (5FU) may provide important clues to the development of effective chemotherapy for 5FU-resistant gastric cancer
methodsFour 5FU-resistant cell lines (MKN45/5FU, MKN74/5FU, NCI-N87/5FU, and KATOIII/5FU) were established by continuous exposure of the cells to progressively increasing concentrations of 5FU for about 1 year. Then, mRNA expression levels of four genes associated with 5FU metabolism, i.e., thymidylate synthase (TS), dihydropyrimidine dehydrogenase, thymidine phosphorylase, and orotate phosphoribosyltransferase, were quantitatively evaluated by real-time reverse transcriptase-polymerase chain reaction. In addition, TS protein expression was measured by Western blot analysis.
resultsAs compared with the parent cell lines, the 5FU-resistant cell lines showed 3.8- to 11.6-fold higher resistance to 5FU, as well as 1.9- to 3.5-fold higher TS mRNA expression and 1.6- to 7.1-fold higher TS protein expression. In contrast, the expressions of other genes did not differ significantly among the cell lines. The cytotoxicity of 5FU was enhanced 2.3- to 2.8 fold by leucovorin (LV) against three of the four 5FU-resistant cell lines.
conclusionsCollectively, LV enhanced the cytotoxicity of 5FU not only against the parent gastric cancer cell lines, but also against the 5FU-resistant cell lines, even those with elevated TS expression levels. These results suggest that clinical studies of a combination of 5FU and LV are warranted in patients who have recurrent gastric cancer after 5FU-based therapy.
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