Abstract
BackgroundFive-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.MethodsCEA protein expression was evaluated by cytofluorimetric and western blot analysis. Relative quantification of CEA mRNA was assessed by real time RT-PCR analysis.ResultsLevels 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.ConclusionThese 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.
Highlights
Five-fluorouracil (FU), mainly associated with leucovorin (L), plays an essential role in chemotherapy of colorectal carcinoma
We decided to investigate the effect of FU + L (FUL), alone or combined with OXA on HT-29 colon cancer cells, using different schedules of the two drugs, i.e. OXA given before FUL (OXA day 1) or OXA given after 1-day exposure to FUL (OXA day 2)
On the contrary, when HT-29 cells were treated with OXA on day 2 (i.e. 1 day after exposure to FUL), the platinum compound did not reduce sensibly the FUL-mediated up-regulation of carcinoembryonic antigen (CEA) expression, which remained on the value of approximately 4-fold increase
Summary
Five-fluorouracil (FU), mainly associated with leucovorin (L), plays an essential role in chemotherapy of colorectal carcinoma. 5-fluorouracil (FU) is considered the reference drug for the treatment of advanced colon cancer It is considered active in the treatment of a number of other common malignancies such breast, gastric and head and neck cancer [1]. Combination therapy appeared to provide better results in terms of response rate and survival, respect to treatment with FU alone [1,2,3,4,5,6,7,8] These clinical trials, did not show a noticeable cure rate or long term survival, and there is a need for the development of new treatment modalities, possibly involving specific immunotherapy. A large variety of tumor-associated antigens (TAAs) has been identified, allowing the development of several tumor vaccines that are currently under investigation [9]
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