does oxaliplatin improve 5-fluorouracil-dependent radiosensitivity?
Department of Tumor Biology, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway. BACKGROUND AND PURPOSE: New chemoradiotherapy regimens for rectal cancer with integration of oxaliplatin with 5-fluorouracil-based therapy are being actively investigated. However, only limited preclinical data are available on oxaliplatin as radiosensitizer in colorectal carcinoma. MATERIALS AND METHODS: A human colorectal carcinoma cell line (HT29) was exposed to ionizing radiation with or without oxaliplatin and/or 5-fluorouracil, upon which clonogenicity and cell cycle profiles were analyzed. HT29 xenografts were treated for two weeks with daily radiation and/or the oral 5-fluorouracil analog capecitabine with or without oxaliplatin once weekly, and tumor volumes were followed for up to 60 days. RESULTS: Pretreatment of HT29 cells with oxaliplatin for 2h, followed by radiation and a 48-h exposure to 5-fluorouracil, resulted in increased radiocytotoxicity, and combination index analysis indica
GROUND AND PURPOSE: New chemoradiotherapy regimens for rectal cancer with integration of oxaliplatin with 5-fluorouracil-based therapy are being actively investigated. However, only limited preclinical data are available on oxaliplatin as radiosensitizer in colorectal carcinoma. MATERIALS AND METHODS: A human colorectal carcinoma cell line (HT29) was exposed to ionizing radiation with or without oxaliplatin and/or 5-fluorouracil, upon which clonogenicity and cell cycle profiles were analyzed. HT29 xenografts were treated for two weeks with daily radiation and/or the oral 5-fluorouracil analog capecitabine with or without oxaliplatin once weekly, and tumor volumes were followed for up to 60 days. RESULTS: Pretreatment of HT29 cells with oxaliplatin for 2h, followed by radiation and a 48-h exposure to 5-fluorouracil, resulted in increased radiocytotoxicity, and combination index analysis indicated synergistic effects. Ionizing radiation and oxaliplatin induced cell cycle G(2)/M phase arr
