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.

Abstract

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.

CONCLUSION:

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.

• Authors: Salvatore P Prete, Mario Turriziani, Maria C Massara, Alessia De Rossi, Pierpaolo Correale, Liana De Vecchis, Francesco Torino, Laura Bonmassar, Angelo Aquino
• Journal: Journal of experimental & clinical cancer research : CR (J Exp Clin Cancer Res) Vol. 27 Pg. 5 (May 19 2008) ISSN: 1756-9966 [Electronic] England
• PMID: 18577244 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Carcinoembryonic Antigen
• Organoplatinum Compounds
• RNA, Messenger
• Oxaliplatin
• Leucovorin
• Fluorouracil

Topics

• Antineoplastic Agents (administration & dosage)
• Carcinoembryonic Antigen (genetics, metabolism)
• Cell Line, Tumor
• Colonic Neoplasms (drug therapy, genetics, metabolism)
• Flow Cytometry
• Fluorouracil (administration & dosage)
• Humans
• Leucovorin (administration & dosage)
• Organoplatinum Compounds (administration & dosage)
• Oxaliplatin
• RNA, Messenger (metabolism)