【摘要】 目的比较基因病毒治疗系统CNHK300-mIFN-γ(以下简称CNHK300-Mγ)与单纯病毒治疗(CNHK300)或基因治疗(AdEasy-mIFN-γ,以下简称AdEasy-Mγ)对裸鼠移植瘤的抑瘤差异。方法观察CNHK300-Mγ、CNHK300和AdEasy-Mγ在裸鼠肝癌SMMC-7721动物模型中的抑瘤差异,并用ELISA法检测血清中mIFN-γ的表达量,HE染色观察肿瘤坏死情况,免疫组织化学染色观察肿瘤内腺病毒外壳蛋白表达情况和肿瘤内微血管生成情况。结果 CNHK300-Mγ具有明显的肿瘤生长抑制作用,与CNHK300、AdEasy-Mγ和对照组的差异均有统计学意义(P<0.05);CNHK300-Mγ组中HE染色肿瘤内见大片坏死,免疫组织化学染色肿瘤内见大量腺病毒外壳蛋白,肿瘤微血管生长明显受抑制,与CNHK300、AdEasy-Mγ和对照组的差异均有统计学意义(P<0.01)。结论基因病毒治疗系统对肿瘤细胞的杀伤能力提高,CNHK300-Mγ能明显抑制肿瘤生长,具有良好的临床应用前景。更多还原

【Abstract】 Objective To investigate the anti-tumor efficacy of a novel gene-viral therapeutic system CNHK300-mIFN-γ(CNHK300-Mγ) in hepatocellular carcinoma(HCC) xenografts. Methods Cancer cells in log phase were subcutaneously injected into the right flanks of BALB/c nude mice,with administration of 5×106 SMMC-7721 per mouse.When SMMC-7721 tumors reached about 50 mm3,mice were allocated randomly into 4 groups: CNHK300-Mγ,CNHK300,AdEasy-Md and control groups(n=16).Five intratumoral injections,once every other day,were carried out in subjects,with a total dosage of 109 pfu per mouse in the virus-treated groups and with 100 μL viral preservation solution per mouse per injection in the control group.On the 3rd and 7th day after treatment,groups of 3 mice were sacrificed for collection of serum by retroorbital puncture.ELISA was used for assessment of mIFN-γ.H&E staining and immunohistochemistry were applied for assessment of tumor necrosis and the expression of adenoviral capsid protein hexon,respectively. Results CNHK300-Mγ exhibited excellent therapeutic efficacy with tumor inhibition rate,which was significantly higher than that in CNHK300,AdEasy-Mγ and control groups(P<0.05).Extensive necrotic foci in pathologic examination were revealed in tumor tissues of CNHK300-Mγ group,compared with those of control group.There were abundant adenoviral capsid protein positive cancer cells in the CNHK300-Mγ group,whereas none was observed in the control group.Meanwhile,significant inhibition of microvessel density was revealed in CNHK300-Mγ group,when compared with those in CNHK300,AdEasy-Mγ and control groups(P<0.05). Conclusion CNHK300-Mγ can effectively suppress HCC growth through direct viral killing effects and inhibition of tumor angiogenesis,holding a splendid future as a potential antitumor agent.更多还原