西罗莫司对人肝癌裸鼠肝脏移植瘤生长的影响

Effects of sirolimus on the growth of transplanted hepatocellular carcinoma

目的探讨西罗莫司（SRL）对人肝癌裸鼠肝脏移植瘤生长的影响。方法建立人肝癌裸鼠肝脏移植瘤模型，使用SRL、他克莫司（FK506）进行干预治疗，采用免疫组织化学方法和图像分析技术检测移植瘤血管内皮细胞生长因子、增殖细胞核抗原的表达和微血管密度，原位末端标记法检测肿瘤细胞凋亡情况。统计学处理采用方差分析或t检验。结果（1）SRL、FK506组和对照组移植瘤质量分别为（352±38）mg、（683±53）mg、（675±45）mg；SRL组移植瘤质量较对照组明显减少（t=10．378，P〈0．01）；FK506组和对照组比较无明显差异（P〉0．05）。（2）SRL组移植瘤血管内皮细胞生长因子和增殖细胞核抗原的表达较对照组明显下调（t值分别为5．753和5．296，P〈0．05），FK506组和对照组比较无明显差异（P〉0．05）。（3）SRL组移植瘤微血管密度较对照组明显减少（t=8．637，P〈0．01）；FK506组和对照组相比无明显变化（P〉0．05）。（4）SRL组移植瘤凋亡指数明显高于对照组（t=11．518，P〈0．05）；FK506对移植瘤凋亡指数无明显影响（P〉0．05）。结论SRL可通过减少肿瘤血管形成、阻止肿瘤增殖、诱导肿瘤细胞凋亡抑制肝癌的生长。

Objective To study the effects of sirolimus （SRL） on the growth of transplanted human hepatocellular carcinoma （HCC） in nude mice. Methods HepG2 cells were Implanted into the liver of nude mice. The implanted mice were then treated with SRL and tacrolimus （FK506）. The expression of vascular endothelial growth factor （VEGF） and proliferating cell nuclear antigen （PCNA） was detected by immunohistology, microvessel density （MVD） was counted by immunostaining with anti-CD34 antibody for endothelial cells. Tumor apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL） assay. Results The tumor weight was （352 ±38） rag, （683± 53） mg and （675± 45） mg in SRL, FK506 and control group respectively. The tumor weight was significantly decreased in SRL group （P 〈 0.01）, and there was no difference between FK506 group and control group. The expression of VEGF and PCNA protein was remarkably down-regulated in SRL group compared to control group （P 〈 0.05）, and it was not significantly different between FK506 group and control group （P 〉 0.05）. Compared to the control group, MVD was significanly decreased in SRL group, and the apoptosis index of tumor cell was significantly higher in SRL group （P 〈 0.01）. Conclusion SRL inhibits transplanted HCC tumor growth by reducing tumor angiogenesis, inhibiting tumor proliferation and inducing tumor apoptosis.