中文摘要：

目的观察α-干扰素（IFN-α）治疗肝癌产生耐药性的过程，探讨其机制。方法裸鼠肝内原位接种裸鼠人肝癌高转移裸鼠模型LCI—D20肿瘤组织，随机分为7组，每组6只。其中治疗组于接种肿瘤后第2天皮下注射给予IFN-α（1．5×10^7U／kg体重／d）20d，治疗组A和B裸鼠于停药后第1和21天分别被处死；治疗组C和D于停药后第21天再次给予同剂量IFN-α（1．5×10^7U／kg体重／d）联合格列卫（100mg／kg体重／d，灌胃）治疗20d。对照组E～G分别在接种肿瘤后第28、48、68天被处死。观察裸鼠体重，肿瘤大小、体积，检测血清血管内皮细胞生长因子（VEGF）浓度、肿瘤组织微血管密度。抽提A、D、E、G各组总RNA做关于血管生成SuperArray基因芯片。结果A～G组肿瘤的大小分别为0．27、1．54、3．22、2．23、0．68、1．93、3．98g，其中组A和组E，组D和组G相比，肿瘤大小差异有统计学意义（P〈0．05）。外周血VEGF浓度组A和组E，组C、D和组G相比差异有统计学意义（P〈0．05）。芯片结果提示在IFN-α治疗过程中，肝癌组织VEGF mRNA和裸鼠血清中的VEGF仍保持较低水平，而PDGF—AA mRNA的表达水平逐渐升高。组A微血管密度显著低于组E，而在组C和组G间差异无统计学意义。HE染色显示治疗组与对照组相比，异常核分裂象增多，肿瘤周围包膜变薄，纤维成分减少。结论肝癌可对IFN-a治疗产生耐药性，可能的机制为肝癌肿瘤血管生成由VEGF依赖转化为PDGF依赖。

英文摘要：

Objective To investigate the chemoresistance of hepatocellular carcinoma （HCC） to interferon a （IFN-α） treatment and to explore the possible mechanism. Methods Nude mice with LCI- D20 were randomized into 4 treatment groups A-D and control groups E- G （n = 6 each group）. IFN-α was administrated subcutaneously at dosages of 1.5 × 10^7 U/（kg. d） for 20 days,then the nude mice in groups A and B were sacrificed at day 28 and 48 respectively;The nude mice in groups C and D received IFN-α （ 1.5 ×10^7 U/kg. d） and Glivec （100 mg/kg, d,p. o, ） combined with IFN-α （1.5 × 10^7 U/kg. d） treatment again at day 48 respectively for 20 days;The nude mice in groups E, F and G were sacrificed at day 28,48,68 respectively. Tumor size and diameter, microvessel density and serum VEGF concentration were recorded. SuperArray cDNA chips about angiogenesis of groups A, D,E and G were used. Results The tumor weight of groups A-G was 0.27,1.54,3.22,2.23,0.68,1.93 and 3.98 g respectively,and there was statistically significant difference between groups A and E, groups D and G （ P 〈0.05）. The serum VEGF concentration of group A and groups C,D was lower than that of group E and group G respectively. The results of cDNA array revealed that during IFN-α treatment process EVGF gene expres- sion maintained low level, whereas PDGF-A gene expression held high level. The microvessel density of group A was lower than that of group E statistically, H＆E staining showed tumor from IFN-α treatment had a more invasive and malignant phenotype. Conclusion Chemoresistance of HCC emerges to IFN-α therapy and this resistance involves vascular regrowth in a PDGF-A independent second wave of angiogenesis.