Synergism in concomitant chemoradiotherapy of cisplatin and oxaliplatin and their liposomal formulation in the human colorectal cancer HCT116 model.

Abstract

BACKGROUND: We choose to test the effect of associating chemo-radiotherapy at 8 h (the highest level of DNA-platinum) and 48 h (the lower level of DNA-platinum) to clarify if irradiation at the maximum DNA-platinum concentration could improve the synergism. MATERIALS AND METHODS: Growth inhibition of the human colorectal cancer cell line HCT116 treated with cisplatin, oxaliplatin, Lipoplatin™ and Lipoxal™ plus gamma-radiation was determined by a colony formation assay. The synergism was evaluated using the combination index method. RESULTS: For 8 h and 48 h exposure to cisplatin or Lipoplatin™, followed by irradiation, drug concentrations higher than IC(50) were found to be synergistic, while a lower than IC(50) concentration was antagonistic. For oxaliplatin, exposure to a concentration above IC(50) for 8 h was synergistic, while the exposure to oxaliplatin (at any concentrations) for 48 h was antagonistic. Lipoxal™ significantly improved synergism compared to its parent drugs. All tested platinum drugs sensitize radiation-treated HCT116 cells by inducing G(2) phase. CONCLUSION: The difference of drug concentrations and the time interval between drug administration and radiotherapy could give different results in chemoradiation therapy.