不同途径应用单纯疱疹病毒胸苷激酶及丙氧鸟苷对裸鼠肝癌模型抑瘤效果的研究

Adenovirus-mediated fransfer of the herpes simplex virus thymidine rinase gene used by several methods

目的 探讨腺病毒介导的单纯疱疹病毒胸苷激酶 (HSV tk)及丙氧鸟苷 (GCV)自杀基因系统通过不同途径应用时的抑瘤效果及粗略的量效关系。 方法 按瘤体内直接注射、尾静脉注射、腹腔内注射的不同途径分为 4组 ,尾静脉注射及腹腔内注射组组内按应用剂量不同各分为 3个亚组 ,分别注射重组腺病毒 (AdrAFPTK) 1× 10 9PFU、1× 10 10 PFU、1× 10 11PFU ,腹腔注射GCV10 0mg·kg-1·d-1后观察瘤体大小变化 ,用RT PCR方法检测瘤体中HSV tk基因片段。 结果 瘤体内直接注射及尾静脉注射 1× 10 11PFU组均观察到明显抑瘤作用 (t为 13 1,12 4,P <0 0 1)及HSV tk基因片段存在 ,尾静脉注射 1× 10 10 PFU组、1× 10 9PFU组及腹腔内注射各亚组均未观察到明显抑瘤作用 (t为 1 8、1 0、2 1、1 1、0 8,P >0 0 5 )及HSV tk基因片段存在。 结论 瘤体内直接注射及高剂量静脉注射途径应用腺病毒介导的HSV tk/GCV自杀基因系统均有明显抑瘤作用 。

Objective To investigate the therapeutic effects of adenovirus-mediated transfer of the herpes simplex virus thymidine rinase gene(HSV-tk) used by several methods and the dose-effect relationship. Methods Diverse doses(1×10 9 PFU, 1×10 10PFU, 1×10 11PFU)of adenovirus-mediated transfer of HSV-tk were given by intraparenchymatous, intravenous and intraperitoneal injection, and ganciclovir (GCV) (100 mg·kg -1·d -1) was injected into the cavity of the peritoneum to treat human hepatocarcinoma. The change of tumors size was observed and the fragments of HSV-tk gene were tested. Results In nude mice after intraparenchymatous injection and high-dose (1×10 11PFU) intravenous injection, the tumors were suppressed significantly (t=13.1,12.4,P<0.01) and lots of fragments of HSV-tk gene were observed. In mice after intraperitoneal injection and low-dose (1×10 9PFU?1×10 10PFU)intravenous injection, no suppressive effect was observed (t=1.8,1.0,2.1,1.1,0.8,P>0.05) with few or without fragments in the tumors. Conclusions Adenovirus-mediated transfer of the HSV-tk by intraparenchymatous or intravenous injection is effective in treatment of hepatocarcinoma in nude mice, but intraperitoneal injection has no therapeutic effect.