Pemetrexed disodium combined with oxaliplatin, SN38, or 5-fluorouracil, based on the quantitation of drug interactions in human HT29 colon cancer cells
| Autor: | Christophe Tournigand, Eric Raymond, Aimery de Gramont, Anne Marie Coudray, Sandrine Faivre, Christian Gespach, Christophe Louvet |
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| Rok vydání: | 2002 |
| Předmět: |
Cancer Research
Guanine Organoplatinum Compounds Cell Survival Colorectal cancer medicine.drug_class medicine.medical_treatment Transplantation Heterologous Pemetrexed Irinotecan Antimetabolite Mice Glutamates Antineoplastic Combined Chemotherapy Protocols medicine Animals Humans Drug Interactions neoplasms Mice Inbred BALB C Chemotherapy business.industry Cancer DNA Neoplasm Neoplasms Experimental medicine.disease digestive system diseases Oxaliplatin Oncology Fluorouracil Colonic Neoplasms Immunology Cancer research Camptothecin Female business HT29 Cells Cell Division Neoplasm Transplantation medicine.drug |
| Zdroj: | International Journal of Oncology. |
| ISSN: | 1791-2423 1019-6439 |
| DOI: | 10.3892/ijo.21.2.361 |
| Popis: | Premetrexed disodium (MTA) is a novel multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. It exhibits a broad spectrum of activity against several human tumor types including colorectal cancer. Therefore, we evaluated the anti-proliferative potential of MTA combined with drugs known to exert therapeutic activity against colon cancer, including 5-fluorouracil, oxaliplatin, and SN38, the active metabolite of irinotecan. The effects of MTA, alone or combined with one of theses 3 drugs, were investigated in parental human HT29 colon cancer cells and in 5-fluorouracil-resistant counterparts HT29-5FU cells. These drugs were administered either simultaneously or sequentially. Functional interactions between MTA, 5-fluorouracil, oxaliplatin, and SN38 were evaluated using median-effect plot analysis. The drug combination and sequence with optimal effects were evaluated in athymic mice bearing human HT29 tumor cell xenografts. Combinations of MTA with 5-fluorouracil required high concentrations to achieved additive and/or synergistic effects. Simultaneous exposure to MTA and oxaliplatin led to synergistic activity in both parental and 5-fluorouracil-resistant human HT29 colon cancer cells, leading to additive antitumor effects and minimal toxicity in athymic mice bearing HT29 cell tumors. Synergism between MTA and SN38 was also observed in both parental and 5-fluorouracil-resistant HT29 cells. These results argue in favor of clinical trials of chemotherapy combining MTA with oxaliplatin or irinotecan (CPT-11), for the treatment of patients with colon cancer. |
| Databáze: | OpenAIRE |
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