Response to 5-fluorouracil of orthotopically xenografted human colon cancers with a microsatellite instability: Influence of p53 status

Response to 5-FU of 5 different human colon cancers (hCC) with a DNA micros atellite instability (MSI), xenografted into nude mice, was analysed accord ing to their p53 status. Two hCC (TC82 and TC71) had a mutated p53 (mutp53) , while two others (TC33 and LoVo) had a wild type p53 (wtp53); the fifth t umour (X17LoVo) originated from the stable transfection of LoVo cells with a dominant mutp53 (273his) vector: All tumours were implanted onto the caec um of nude mice to induce orthotopic growth of hCC. 5-FU was administered a t 40 mg/kg per day for 5 consecutive days. A significant growth inhibition of TC82 and TC71 tumours (of 68 and 60%, p <0.05 and <0.01 respectively) wa s observed, whereas 5-FU had no effect on TC33 and LoVo. Moreover the mutp5 3 transfected tumour, X17LoVo, displayed significant sensitivity to 5,FU (p <0.05). This suggests that distinct genetic alterations influence different ly the response of hCC to this antimetabolite.