Combination of oxaliplatin and irinotecan on human colon cancer cell lines: activity in vitro and in vivo
| Autor: | Isabelle Hennebelle, Sylvie Guichard, Roland Bugat, Stéphanie Arnould, Pierre Canal |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Oncology
Cancer Research DNA Repair Organoplatinum Compounds Apoptosis DNA Adducts Mice Tumor Cells Cultured Drug Interactions Pharmacology (medical) Enzyme Inhibitors biology Reverse Transcriptase Polymerase Chain Reaction Chemistry RNA-Binding Proteins Drug Synergism Xeroderma Pigmentosum Group A Protein DNA-Binding Proteins Oxaliplatin Colonic Neoplasms Female Poly(ADP-ribose) Polymerases medicine.drug medicine.medical_specialty Poly ADP ribose polymerase Antineoplastic Agents Irinotecan In vivo Internal medicine medicine Animals Humans neoplasms Pharmacology Topoisomerase Proteins Endonucleases Xenograft Model Antitumor Assays digestive system diseases Cell culture biology.protein Cancer research Camptothecin Drug Screening Assays Antitumor Topoisomerase I Inhibitors ERCC1 |
| Zdroj: | Anti-Cancer Drugs. 12:741-751 |
| ISSN: | 0959-4973 |
| Popis: | The in vitro and in vivo combination of oxaliplatin and irinotecan was investigated in a panel of four human colon cancer cell lines and their counterpart xenografts. In vitro and in vivo experiments demonstrated a synergistic or additive interaction in three cell lines (HCT-116, HCT-8 and HT-29) and an antagonism in SW-620 cells. Since there were clearly opposite interactions depending on the cell line, we further investigated cellular determinants possibly involved in the interaction between the two drugs in HCT-8 and SW-620 cells. Irinotecan slowed down the early platinum-DNA adducts repair (1 h after oxaliplatin exposure) in the presence of irinotecan only in HCT-8 cells (p=0.03, n=3). Moreover, a decrease of the expression of two proteins of the nucleotide excision repair (NER) system, ERCC1 and XPA, was observed. None of these effects was seen in SW-620 cells. Irinotecan induced apoptosis with an increase of poly(ADP-ribose) polymerase (PARP) cleavage in SW-620 cells (60 versus 7% basal level). Pretreatment of these cells with oxaliplatin abolished the increase in PARP cleavage induced by irinotecan (29%). In HCT-8 cells, a very little PARP cleavage was observed whatever the drug treatment. The persistence of platinum-DNA adducts in the presence of irinotecan could be due to a direct impact of irinotecan on NER gene expression or to an indirect effect on topoisomerase I activity. Complementary studies are required to determine if the cellular parameters identified in this study could be translated at the clinical level to predict clinical response after combined treatment with oxaliplatin and irinotecan in humans. |
| Databáze: | OpenAIRE |
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