α干扰素和5-氟尿嘧啶对肝癌切除术后转移复发抑制作用的实验研究

Effects of interferon-α and 5-fluorouracil on recurrence and metastasis of hepatocellular carcinoma after tumor removement in nude mice

目的研究α干扰素(interferon-α,IFN-α)和5-氟尿嘧啶(5-fluorouracil,5-FU)在肝癌转移模型中对肿瘤切除术后转移和复发的影响。方法裸鼠人肝癌转移模型(LCI-D20)40只,随机分成4组即对照组(生理盐水)、干扰素组(IFN-α2a)、5-FU组和联合组(5-FU与IFN-α2a)。观察肝癌切除后肿瘤复发、肝内播散及肺转移,检测复发瘤血管生成相关指标(MVD、VEGF、bFGF和SMA),并检测血清AFP。结果对照组、干扰素组、5-FU组和联合组肝内复发率分别为100%、90%、100%和80%;肝内出现播散灶率分别为100%、60%、70%和10%;与对照组比较,干扰素组和联合组复发瘤体积、肝内播散灶数量、肺转移率和转移灶数量均明显减少(P<0.05);两药联合应用对抑制肿瘤转移和复发有协同效应;干扰素对肝癌血管形成有良好的抑制作用,与对照组及5-FU组比较有统计学意义(P<0.05)。结论干扰素和5-FU均可抑制肝癌术后肿瘤复发与转移,二者联用有协同作用。

Objective：To investigate the effects of interferon-α and 5-fluorouracil on inhibiting metastasis and recurrence of hepatocellular carcinoma （HCC） after the tumor removement in nude mice. Methods：Nude 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 （ IFN-α2b）, 5-FU treatment group and combined treatment group（ both 5-FU and IFN-α2b）. Drugs were given after tumor removment. Then, the size of recurrence tumor were measured and the presence of intrahepatic dissemination and lung metastasis was recorded, at the same time , MVD,VEGF,bFGF and SMA of the recurrence tumors and serum AFP were measured. Results：The rates of tumor recurrence were 100% ,90%, 100% and 80% in control, interferon group, 5-FU group and combined treatment group, respectively. Compared with control, the size of main recurrence lesion , 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 combined treatment group（ P 〈 0. 05 ）. Compared to the control, the number of intrahepatic dissemination and lung metastatic ratio in IFN group and combined treatment group were reduced. A decreases of MVD ,VEGF and SMA were observed in administration of interferon groups compared with that in unuse of interferon-α groups. Conclusions： Interferon-α is capable of inhibiting metastasis and recurrence of HCC after tumor removement in nude mice which exerts its effect by inhibiting tumor angiogenesis. There is a synergistic action between interferon-α and 5-FU in inhibiting the metastasis and recurrence of HCC in nude mice.