逆转录病毒介导HSV-TK基因结合更昔洛韦对裸鼠膀胱癌模型的抑癌作用

Retrovirus-mediated HSV-TK gene combined with GCV therapy for experimental bladder cancer

目的研究利用逆转录病毒介导单纯疱疹病毒胸苷激酶(HSVTK)基因结合抗病毒药更昔洛韦(GCV)对裸鼠膀胱癌模型的治疗作用。方法构建HSVTK基因逆转录病毒重组体,转染PA317包装细胞后获得相应病毒,分3组进行动物实验。A组7个肿瘤,膀胱癌细胞MBT2种植小鼠皮下形成裸鼠动物模型,用带HSVTK基因的逆转录病毒瘤内注射并腹腔内注射GCV。B组6个肿瘤,用转导HSVTK基因的膀胱癌细胞形成裸鼠膀胱癌模型并腹腔内注射GCV。C组6个肿瘤,用膀胱癌细胞MBT2种植小鼠皮下形成裸鼠膀胱癌模型,并注射生理盐水。比较3组治疗后10d、20d肿瘤的体积变化情况。结果GCV治疗10d后,A、B和C组肿瘤平均体积分别为(55.37±4.52)、(49.77±4.15)、(146.27±10.46)mm3,A、B组与C组比较差异有统计学意义(P<0.01),A、B组间差异无统计学意义(P>0.05)。20d后A、B和C组肿瘤平均体积分别为(186.75±8.14)、(72.50±6.70)、(441.76±41.80)mm3,3组间两两比较差异均有统计学意义(P<0.01)。结论利用逆转录病毒介导HSVTK基因结合GCV治疗可显著抑制裸鼠膀胱癌的生长,并使肿瘤获得部分消退。

Objective To determine the efficacy of retrovirus-mediated HSV-TK gene transfer and GCV in a BALB/c mice model with urinary bladder transitional cell carcinoma. Methods A replication defective retroviral vector containing HSV-TK gene was used. In vivo experimental animals were divided into 3 groups. In group A ,7 tumors were induced in BALB/c mice by subcutaneous injection of MBT-2 transitional cell carcinoma （TCC） ;the virus was directly injected into the tumor and the animals received intraperitoneal GCV. In group B, 6 tumors were induced in BALB/c mice by subcutaneous injection of transferred HSV-TK gene TCC and the animals received intraperitoneal GCV. In group C,6 tumors were induced in BALB/c mice by subcutaneous injection of MBT-2 TCC and the animals received intraperitoneal normal saline. Tumor-volume measurement was performed in these 3 groups 10 d and 20 d after treatment, and the volume changes were compared among the 3 groups. Results In vivo experiment indicated that the mean tumor volume of group A [ MBT-2 group, （55.37 ± 4.52） mm^3] and group B [ MBT-2/HSV-TK group, （49.77± 4.15）mm^3 ] was reduced significantly compared with that of group C [ control group, （146.27 ± 10.46） mm^3] （ P 〈 0.01 ） 10 d after treatment with GCV ; but the difference of the tumor volume between groups A and B was not significant （ P 〉 0.05 ）. At 20 d after treatment, the mean tumor volume of group A [ （ 186.75 ± 8.14 ） mm^3 ] and group B [ （72.50 ± 6.70） mm^3] was also reduced compared with that of group C [ （441.76 ± 41.80） mm^3 ] （ P 〈 0.01 ）. There was also significant difference of tumor volume between groups A and B （P 〈0.01 ）. Conclusions Treatment of pLNS-TK retrovirus combined with GCV can inhibit significantly the tumor growth of bladder cancer in mice, and the tumor can be partially resolved with this treatment.