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 microsatellite instability (MSI), xenografted into nude mice, was analysed according 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 tumour (X17LoVo) originated from the stable transfection of LoVo cells with a dominant mutp53 (273his) vector. All tumours were implanted onto the caecum of nude mice to induce orthotopic growth of hCC. 5-FU was administered at 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) was observed, whereas 5-FU had no effect on TC33 and LoVo. Moreover, the mutp53 transfected tumour, X17LoVo, displayed significant sensitivity to 5-FU (p < 0.05). This suggests that distinct genetic alterations influence differently the response of hCC to this antimetabolite.
Pocard
M
M
ICRF-Colorectal Cancer Unit, Saint Mark's Hospital, Harrow, Middlesex, United Kingdom.
Bras-Gonçalves
R
R
Hamelin
R
R
Northover
J
J
Poupon
M F
MF
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D002432:Cecum; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D005799:Genes, Dominant; D016158:Genes, p53; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D018895:Microsatellite Repeats; D009154:Mutation; D009368:Neoplasm Transplantation; D010641:Phenotype; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000637:transplantation
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil