局部应用ADV-TK基因防止裸鼠肝癌切除后转移复发的实验研究

目的 探讨ADV-TK基因局部应用防止裸鼠肝癌根治性切除后转移复发的机制.方法 建立裸鼠肝癌模型后,行根治性切除,同时各组(对照组10只、肝断面注射基因组11只、腹膜后注射基因组11只)分别注射ADV-TK基因50μl,24h后腹腔注射更昔洛韦50μg/10g体重.治疗组各取1只注射含绿色荧光蛋白标记基因的裸鼠,24h后处死裸鼠,观察基因转染情况.6周后,处死其余裸鼠,分别检查肝内及腹腔内其他脏器、肺等转移、复发情况,测量复发肿瘤的体积.结果 (1)各器官均可见该基因转染.(2)肝内复发情况:复发肿瘤数目、体积及涉及肝叶数对照组为(8.7±6.5)、(2933±597)mm3、(4.3±2.2),肝断面注射基因组为(0±0)、(0±0)mm3、(0±0),腹膜后注射基因组为(2.2±1.3)、(265±109)mm3、(2.1±1.3),基因注射组各指标明显降低,分别与对照组比较,差异有统计学意义(x2=3.05,P<0.01,x2=5.32,P<0.01).(3)肿瘤的肺及远处转移情况:肺转移率、涉及器官数和AFP值对照组为(10/10)、(7.2±5.3)、(1322±702),肝断面注射基因组为(2/10)、(3.2±1.5)、(322±102),腹膜后注射基因组为(1/10)、(1.8±1.2)、(268±133),分别与对照组比较,差异有统计学意义(X2=4.33,P<0.01,x2=7.15,P<0.01).结论 ADV-TK基因局部注射可以转染裸鼠各内脏器官并可以抑制肝癌根治性切除后的转移、复发.

ADV-TK gene inhibits recurrence and metastasis of hepatocellular carcinoma after curative resection in a nude mouse model

Objective To evaluate the effect of ADV-TK gene in its inhibition of the recurrence and metastasis of hepatocellular carcinoma after curative resection in a nude mouse model. Methods In the two experimental groups, GFP-labelled ADV-TK gene transfection was determined 24 h after injection in one-each mouse. Nude mice with inplanted intrahepatic hepatocellular carcinoma underwent curative tumor resection, in the end of the operation ADV-TK gene was injected in incisional margin (11 mice) or retroperitoneally (11 mice). Ganciclovir at a dosage of 50 μg/10 g bw was given in the next day after resection. Mice in control group did not receive ADV-TK gene injection. After six weeks, mice were sacrificed. Results 1. It was showed that organs were all transfected by ADV-TK gene.2. Compared with the control group in which the recurrent tumor number of (8.7±6.5) ,tumor volume of (2933±597) mm3, and recurrence involved liver lobes of (4.3±2.2), that was (0.0±0.0), (0.0±0.0) mm3, and (0.0±0.0)(X2 = 3.05 all P<0.01) in incisional margin gene injection group, and (2.2±1.3), (265±109) mm3, and (2.1±1.3) (X2= 5.32, all P<0.01 ) respectively in intraperitoneally gene injection group.3. Compared with the control group in which the lung metastasis rate of (10/10)、number of distant organ involved by metastasis of (7.2±5.3 ), and serum AFP level of (1322±702), that was (2/10) , (3.2±1.5) and (322±102), (X2=4.33, all P<0.01) in incisional margin group, and ( 1/10)、( 1.8±1.2 ), and (268±133 ) ( X2=7.15, all P<0.01 ) in retroperitoneal group, respectively. Conclusions ADV-TK gene inhibits recurrence and metastasis of HCC after curative resection in this nude mouse model.