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我们成功开展了携带单纯疱疹Ⅰ型病毒胸腺嘧啶激酶基因(Herpes simplex virus thy-midine kinase,HSV-tk)的复制缺陷型重组腺病毒Ad(HSV-tk)结合使用GCV治疗C 57 BL/6小鼠B 16黑色素瘤的离体及动物试验。导入了HSV-tk基因的B16细胞对GCV的杀伤作用高度敏感,IC_(50)约为0.1μg/ml;感染与未感染Ad(HSV-tk)的B 16细胞混合后,可观察到显著的细胞毒杀伤作用——“旁观者效应”。Ad(HSV-tk)直接注入C57BL/6小鼠已建成的B16黑色素瘤内,结合连续6 d腹腔给予GCV,肿瘤结节出现萎缩坏死现象,大小仅为对照组的1/25。灵敏的RT-PCR检测结果表明:瘤内注射Ad(HSV-tk)后,腺病毒的扩散范围是有限的,HSV-tk基因的表达局限于肿瘤组织内。因此,Ad(HSV-tk)/GCV疗法可能为黑色素瘤等恶性实体瘤的治疗提供了一种较为有效、安全的选择方案。
We successfully performed replication-defective adenovirus Ad (HSV-tk) combined with Herpes simplex virus thymidine kinase (HSV-tk) combined with GCV to treat C 57 BL/6 small In vitro and animal studies of murine B 16 melanoma. HSV-tk gene-introduced B16 cells are highly sensitive to the killing effect of GCV, IC 50 is approximately 0.1 μg/ml; significant changes can be observed after infection with B 16 cells not infected with Ad (HSV-tk). Cytotoxicity - “bystander effect.” Ad (HSV-tk) was directly injected into the established B16 melanoma of C57BL/6 mice. GCV was administered intraperitoneally for 6 consecutive days. Tumor nodules showed atrophy and necrosis. The size was only 1/25 of the control group. Sensitive RT-PCR results showed that the adenoviral diffusion was limited after intratumoral injection of Ad (HSV-tk), and the expression of HSV-tk gene was confined to the tumor tissue. Therefore, Ad (HSV-tk)/GCV therapy may provide a more effective and safe alternative for the treatment of malignant solid tumors such as melanoma.