5-fluorouracil concentration in blood, liver and tumor tissues and apoptosis of tumor cells after preoperative oral 5′-deoxy-5-fluorouridine in patients with hepatocellular carcinoma

Abstract

Aim: To study the levels of 5-fluorouracail (5-FU) in plasma, liver and tumor in patients with hepatocellular carcinoma after oral administration of 5′-deoxy-5-fluorouridine (5′-DFUR). Methods: Thirty-nine patients with hepatocellular carcinoma were treated with oral 5′-DFUR for more than 4 d before operation. The contents of 5-FU in plasma, liver and tumor were measured by high performance liquid chromatography (HPLC) and apoptosis of tumor cells was evaluated by in-situ TUNEL after resection of tumor. Results: The concentrations of 5-FU were 1.1 μg/mL, 5.6, 5.9, and 10.5 μg/g in plasma, the liver tissue, the center of tumor and the periphery of tumor, respectively. 5-FU concentration was significantly higher in the periphery of tumor than that in the liver tissue and the center of tumor (10.5±1.6 μg/g vs 5.6±0.8 μg/g, t = 21.38, P<0.05; 10.5±1.6 μg/g vs 5.9±0.9 μg/g, t = 20.07, P<0.05). 5-FU level was significantly lower in plasma than that in the liver and the tumor (1.1±0.3 μg/mL vs 5.6±0.8 μg/g, t = 19.63, P<0.05; 1.1±0.3 μg/mL vs 10.5±1.6 μg/g, t= 41.01, P<0.05). Apoptosis of tumor cells was significantly increased after oral 5′-DFUR compared to the control group without 5′-DFUR treatment. Conclusion: There is a higher concentration of 5-FU distributed in the tumor compared with liver tissue and apoptosis of tumor cells is increased following oral 5′-DFUR compared with the control group. The results indicate that 5′-DFUR is hopeful as neo-adjuvant chemotherapy to prevent recurrence after resection of hepatocellular carcinoma. © 2005 The WJG Press and Elsevier Inc. All rights reserved.