Combined effects of 5-fluorouracil, folinic acid and oxaliplatin on the expression of carcinoembryonic antigen in human colon cancer cells: pharmacological basis to develop an active antitumor immunochemotherapy.
BACKGROUND
Five-fluorouracil (FU), mainly associated with leucovorin (L), plays an essential role in chemotherapy of colorectal carcinoma. Moreover, FU +/- L has been found to increase the expression of tumor-associated carcinoembryonic antigen (CEA), that may be an important target in therapeutic protocols of active specific immunotherapy. FU + L (FUL) are frequently combined with oxaliplatin (OXA) in advanced colon cancer patients. Thus, we investigated whether FUL in combination with OXA according to 2 different schedules may influence CEA expression in human colon cancer cells in vitro.


METHODS
CEA protein expression was evaluated by cytofluorimetric and western blot analysis. Relative quantification of CEA mRNA was assessed by real time RT-PCR analysis.


RESULTS
Levels of CEA protein and transcript were found to be higher in FUL-treated cells than in controls. However, when target cells were exposed to OXA before but not after FUL treatment, the up-regulation of CEA was partially inhibited.


CONCLUSIONS
These results suggest that target cells must be exposed to OXA after but not before treatment with the fluoropyrimidine in order to exploit drug-induced up-regulation of CEA. This finding appears to provide useful information to design chemo-immunotherapy protocols based on FUL + OXA, combined with host's immunity against CEA directed cancer vaccines.
Prete
Salvatore P
SP
Department of Neuroscience, Section of Pharmacology and Medical Oncology, University of Rome, Tor Vergata, Via Montpellier, 1, 00133 Rome, Italy. salvatore.prete@uniroma2.it
Turriziani
Mario
M
Massara
Maria C
MC
De Rossi
Alessia
A
Correale
Pierpaolo
P
De Vecchis
Liana
L
Torino
Francesco
F
Bonmassar
Laura
L
Aquino
Angelo
A
D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage*; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin; D012333:RNA, Messenger / Q000378:metabolism
D000970:Antineoplastic Agents; D002272:Carcinoembryonic Antigen; D009944:Organoplatinum Compounds; D012333:RNA, Messenger; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil