经门静脉注射重组p53腺病毒治疗肝转移肿瘤的实验研究

Treatment of mouse liver metastasis by intraportai injection of Adv-p53

目的观察经门静脉注射重组p53腺病毒(Adv-p53)对肝转移肿瘤的治疗作用。方法通过门静脉注射2×105个MCA-205肿瘤细胞建立小鼠肝转移肿瘤模型,同时将脾脏移植到皮下,作为反复多次向门静脉注射的途径。经门静脉注射不同剂量Adv-p53,注射等体积的平衡盐水或相同剂量的对照腺病毒Adv-CMV作为对照,第21天检查肝脏重量和肝脏转移结节数。结果经门静脉注射1×108 pfu Adv-p53组的肝脏重量为(1.20±0.34)g,明显低于门静脉注射同剂量Adv-CMV组(P<0.05);肝脏转移结节数目为(9.0±9.9)个,明显少于Adv-CMV组(P<0.05)。Adv-p53抑制肝转移肿瘤形成的作用具有剂量效应。在门静脉注射肿瘤细胞的第5天,肝转移肿瘤已经形成,门静脉注射1×108 pfu Adv-p53组的肝脏重量为(1.22±0.09)g,明显低于Adv-CMV组(P<0.05),肝脏转移结节数目(5.5±3.5)明显少于Adv-CMV组(113.2±5.8,P<0.05)。反复多次门静脉注射Adv- p53,可以加强这一抗肿瘤效果。结论通过门静脉系统应用Adv-p53是治疗肝转移肿瘤的有效方法。

Objective To investigate the anti-tumor effect of intraportal administration of Adv-p53 in the treatment of the liver metastasis in mice. Methods 2 × 10^5 of MCA-205 cells were injected into the mouse portal vein to establish a routine liver metastasis model. The spleen was transpositionad subcutaneously to enable the administration of Adv-p53 continually into the portal system. Different doses of Aclv-p53 were injected intraportally, while HBSS and Adv-CMV were injected intraportaly in the control group. Tumors in the liver were examined on clay 21 after Adv-p53 administration. Results The liver weight in the Aclv-p53 treated mice on clay 0 group （ 1.20 ±~ 0. 34 g） was significantly less than that in the Aclv-CMV group （2.59 ± 0.48 g,P 〈 0.05 ）. The number of metastatic nodules in the Adv-p53 treated mice on day 0 group （ 9.0 ± 9.9 ） was significantly less than that in the Adv-CMV group （ 57.1 ± 11.3, P 〈 0.05 ）, indicating that intraportal administration of Adv-p53 inhibited the formation of liver metastasis. This anti-tumor effect was in a dose-dependent manner. After the liver metastasis was formed, Adv-p53 was administered intraportally. The liver weight in the Adv-p53 treated mice on day 5 group （ 1.22 ± 0.09 g） was significantly less than that in the Adv-CMV group （3.98 ± 1.01 g,P 〈0.05）. The number of metastatic nodules in the Aclv-p53 treaad mice on clay 5 group （ 5.5 ± 3.5 ） was significantly less than that in the Aclv- CMV group （ 113.2 ± 5.8, P 〈 0.05 ）. Repeatedly intraportal administration of Adv-p53 Could enhance this anti-tumor effect. Conclusion Local administration of Adv-p53 into the portal system would be a useful strategy for the liver metastasis treatment.