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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 investigate the effect of rapamycin on the growth of orthotopic transplanted human hepatocellular carcinoma in nude mice and its mechanism. Methods Twenty-two human hepatocellular carcinoma xenografts were established and randomly divided into blank control group, FK506 group, conventional rapamycin group and high dose group. The changes of tumor volume were observed after two weeks of treatment. The expression of proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma was detected by immunohistochemistry. Results The average volume of tumor in control group, FK506 group, rapamycin group and high dose group were (310.15 ± 40.16), (605.59 ± 116.23), (99.19 ± 15 .27), (151.61 ± 27.81) mm3. Compared with the control group, the tumor volume of the conventional and high-dose Rapa groups was significantly reduced, the expression of PCNA and VEGF were significantly decreased (P <0.01); the tumor volume of the FKS06 group was significantly increased compared with the control group, the difference There was statistical significance (P <0.01). There was no significant difference in the expression of PCNA and VEGF between the two groups (P> 0.01). Conclusion Rapamycin can significantly inhibit the growth of hepatocellular carcinoma and its mechanism may be to inhibit the malignant proliferation of liver cancer cells and the production of VEGF.