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

Salvatore P Prete¹ , Mario Turriziani² , Maria C Massara¹ , Alessia De Rossi¹ , Pierpaolo Correale³ , Liana De Vecchis¹ , Francesco Torino⁴ , Laura Bonmassar⁵ and Angelo Aquino¹

¹Department of Neuroscience, Section of Pharmacology and Medical Oncology, University of Rome, "Tor Vergata", Via Montpellier, 1. 00133 Rome, Italy

²Department of Internal Medicine, University of Rome "Tor Vergata", Rome, Italy

³Oncopharmacology Center, School of Medicine, University of Siena, Italy

⁴Division of Medical Oncology, San Filippo Neri Hospital, Rome, Italy

⁵Istituto Dermopatico dell'Immacolata (IDI, IRCCS), Rome, Italy

author email corresponding author email

Journal of Experimental & Clinical Cancer Research 2008, 27:5doi:10.1186/1756-9966-27-5


Published:	19 May 2008

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.