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


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.


CONCLUSIONS
The difference of drug concentrations and the time interval between drug administration and radiotherapy could give different results in chemoradiation therapy.
Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Québec, Canada.
Thititip
T
Tippayamontri
Rami
R
Kotb
Benoit
B
Paquette
Léon
L
Sanche
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D059248:Chemoradiotherapy / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D004357:Drug Synergism; D005720:Gamma Rays / Q000627:therapeutic use; D045325:HCT116 Cells; D006801:Humans; D008081:Liposomes; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin
D000970:Antineoplastic Agents; D008081:Liposomes; D009944:Organoplatinum Compounds; C503131:lipoplatin; D000077150:Oxaliplatin; D002945:Cisplatin