High Glucose Modulates Antiproliferative Effect and Cytotoxicity of 5-Fluorouracil in Human Colon Cancer Cells
| العنوان: | High Glucose Modulates Antiproliferative Effect and Cytotoxicity of 5-Fluorouracil in Human Colon Cancer Cells |
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| المؤلفون: | Ching-Wen Huang, Yi-Shing Ma, Suh-Hang Hank Juo, I-Ping Yang, Jaw-Yuan Wang, Hsiang-Lin Tsai |
| المصدر: | DNA and Cell Biology. 33:64-72 |
| بيانات النشر: | Mary Ann Liebert Inc, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | DNA Replication, Original Research ArticlesOrganelles/Autophagy/Apoptosis, Colorectal cancer, Tetrazolium Salts, Apoptosis, Biology, Flow cytometry, chemistry.chemical_compound, Annexin, Cell Line, Tumor, Genetics, medicine, Humans, Cytotoxicity, Molecular Biology, Cell Proliferation, medicine.diagnostic_test, Cell growth, Cell Biology, General Medicine, Flow Cytometry, medicine.disease, Glucose, chemistry, Fluorouracil, Hyperglycemia, Colonic Neoplasms, Immunology, Cancer research, Growth inhibition, Deoxyuracil Nucleotides, medicine.drug |
| الوصف: | 5-Fluorouracil (5-FU)-based chemotherapy is widely used for the treatment of colorectal cancer (CRC). While optimal doses of 5-FU are generally established based on a patient's estimated body surface area, the plasma concentrations of 5-FU vary among patients. In addition, hyperglycemia in patients with CRC has been reported as a risk factor in poor prognosis. The aim of the present study was to investigate whether hyperglycemia affects antiproliferative effect of 5-FU on the human colon cancer cells (SW480, SW620, LoVo, and HCT116). Growth inhibition of 5-FU was accessed by WST-8 assay. The effect of high glucose (HG, 15 mM) and 5-FU on the cellular proliferation was evaluated by flow cytometry analysis using 5-ethynyl-2′-deoxy-uridine (EdU) incorporation plus 7-AAD. Cell death was determined by flow cytometry using Annexin V-FITC and PI. The results showed that HG, compared to physiological normal glucose (NG) concentration (5 mM), leads to increased cell proliferation and increased GI50 of 5-FU in the four colon cancer cell lines. When the cells were pretreated with a low-dose 5-FU in NG condition, subsequent HG treatment eliminated inhibitory effect of 5-FU in cancer cell growth. In the presence of 5-FU (0.5 μg/mL for LoVo and HCT116; 1 μg/mL for SW480 and SW620), culture with HG for 72 h does not significantly altered cell cycle profile in the four cell lines but significantly increased DNA replication in SW620 (21%) and LoVo (17%). Flow cytometric analysis showed that HG protects cells against 5-FU-induced cell death in SW480. Finally, HG did not alter intracellular level of reactive oxygen species (ROS), although 5-FU indeed induced higher intracellular level of ROS. In conclusion, HG attenuates growth inhibition of 5-FU and our results indicate that decreased cell death and increased DNA replication may account for the attenuating effect of a HG environment on 5-FU-induced tumor growth inhibition. |
| تدمد: | 1557-7430 1044-5498 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e284344b7b134587433adc38fc964654 https://doi.org/10.1089/dna.2013.2161 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e284344b7b134587433adc38fc964654 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15577430 10445498 |
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