雷帕霉素对人肝癌裸鼠原位移植瘤生长的抑制作用

Rapamycin inhibited the growth of hepatocellular carcinoma in nude mice

目的探讨雷帕霉素对人肝癌裸鼠原位移植瘤生长的影响及其机制。方法建立人肝癌棵鼠肝原位移植瘤模型32只,随机分为空白对照组、FK506组、雷帕霉素常规剂量组和高剂量组。用药两周后观察肿瘤体积的变化,免疫组织化学法检测肝癌组织中增殖细胞核抗原(PCNA)、血管内皮细胞生长因子(VEGF)的表达。结果对照组、FK506组、雷帕霉素常规剂量组、高剂量组平均肿瘤体积分别为:(310．15±40．16)、(605．59±116．23)、(99．19±15．27)、(151．61±27．81) mm3。与对照组相比,雷帕常规剂量组及高剂量组肿瘤体积明显缩小,PCNA、VEGF的表达均显著下调(P<0．01);FKS06组肿瘤体积与对照组相比明显增大,差异有统计学意义(P<0．01),PC- NA、VEGF的表达与对照组相比差异无统计学意义(P>0．01)。结论雷帕霉素具有显著抑制肝癌生长的作用,其机制可能是抑制了肝癌细胞的恶性增殖及VEGF的产生。

Objective To study the antitumor effort of rapamycin on hepatocellular carcinoma and the relevant mechanism. Methods Nude mice bearing orthotopic xenografty human HCC were randomly divided into 4 groups： control group, tacrolimus group, rapamycin group, rapamycin high dose group. The effect on the tumor growth was evaluated using tumor volume after 2 weeks. PCNA and VEGF expression in liver cancer tissue was detected by using immunohistochemistry. Results The tumor volume was （310.15 ± 40.16）, （605.59 ± 116.23）, （99.19 ± 15.27）, （151.61 ± 27.81） mm^3 in control, tacrolimus, rapamycin and rapamycin high dose groups respectively. The tumor volume was significandy decreased in rapamycin group and rapamycin high dose group, but increased in tacrolimus group as compare with control group. The expression of PCNA and VEGF was downregulated in rapamycin group and rapamycin high dose group as compare with control group. Conclusion The growth of HCC in the nude mice was inhibited when the animals were exposed to rapamycin but enhanced when exposed to tacrolimus. The antitumor effort of rapamycin attributes to the retardation of tumor cell growth and the downregulation of VEGF expression probably.