Effects Of Interferon-α And 5-Fluorouracil On Recurrence And Metastasis Of Hepatocellular Carcinoma After Tumor Removement In Nude Mice

ObjectiveTo investigate the effects of interferon-a and 5-Fluorouracil on inhibiting metastasis and recurrence of hepatocellular carcinoma (HCC) after the tumor removement in nude mice. MethodsNude mice bearing orthotopic xenografty highly metastatic model HCC(LCI-D20) were randomly divided into 4 groups, they were control group (saline solution), interferon treatment group (Intefen), 5-FU treatment group and combined treatment group(both 5-FU and Intefen). Operation of tumor was performed at 10th day after tumor implantation in 40 nude mice. Drugs were given at the next day after operation. Interferon-a was administered subcutaneously at doses of 3×10~5U/day. 5-FU was injected through abdominal cavity at a dose of 30mg ? kg"1 ? day"1. The mice were sacrificed 36 days after drug treatment. The size of recurrence of tumor were measured and the presence of intrahepatic dissemination and lung metastasis was recorded, at the same time , intratumoral microvessel density(MVD), vascular endothelial growth factor(VEGF),basic fibroblast growth factor (bFGF) , smooth muscle actin (SMA) and serum AFP were measured. ResultsThe rate of tumor recurrence was 100%, 90%,100% and 80% in control, interferon group, 5-FU group and combination group, respectively. The size of main recurrence lesion was 1835.05±70.31mm~3,448.18±58.60mm3> 359.22±36.15mm3 and 21.92±2.90mm\ respectively. The volume of recurrence tumor significantly decreased in treatment groups compared with control(P<0.05) . Compared to 5-FU treatment group and interferon treatment group, the recurrence lesion decreased in combination group(P<0.05).Compared to the control, the number of intrahepatic dissemination and lung metastatic ratio in treatment groups were reduced (6.20±1.31 versus 1.90±1.73, 2.30±1.83, 0.20±0.63 and 100% versus 10%,60%,0). A decrease of MVD ,VEGF and SMA was observed in administration of interferon-a groups compared with that in unuse of interferon-a groups, at the same time, bFGF was found no difference between each group. Serum AFP was 101.01±9.52 ng/mk 62.21 ± 6.77ng/mk 42.96±9.99 ng/ml and 29.83±5.70ng/ml in control, interferon treatment group, 5-FU treatment group and combination group, respectively. ConclusionsInterferon-a are capable of inhibiting metastasis and recurrence of HCC after tumor removement in nude mice which exerts its effect by inhibiting tumor angiogenesis. The effect of 5-FU on inhibiting metastasis and recurrence of HCC is uncertain .There was synergistic action between interferon-a and 5-FU in inhibiting the metastasis and recurrence of HCC in nude mice.