mTOR抑制剂对大鼠肝癌生长抑制作用的研究

发布时间：2018-08-13 10:39

【摘要】：目的探讨m TOR抑制剂对大鼠肝癌的抑制作用及其机制。方法将肝癌细胞植入同源大鼠的肝脏,然后用m TOR抑制剂西罗莫司治疗4周。用磁共振成像监测肿瘤生长情况,通过微脉管密度和血管铸型等体内实验及细胞增殖、微管形成及主动脉环化分析等体外实验评估西罗莫司抗血管生成和抑癌效果。结果西罗莫司治疗组大鼠与对照组相比生存时间明显延长、肿瘤体积小、肝细胞转移和腹水少。西罗莫司还降低了瘤内微血管密度并导致肿瘤广泛性坏死。内皮细胞增殖被抑制所需的西罗莫司浓度低于肝癌细胞。m TOR抑制剂明显抑制微管形成及动脉环的血管发芽新生。西罗莫司治疗的肿瘤中血管生成减少,反而出现套叠式血管生成。结论 m TOR抑制剂抑制了肝癌细胞生长,并主要通过抗血管生成作用延长了荷瘤大鼠生存期。m TOR抑制剂具有治疗肝癌的潜能。
[Abstract]:Objective to investigate the inhibitory effect of m TOR inhibitor on hepatocellular carcinoma in rats and its mechanism. Methods Hepatocellular carcinoma cells were implanted into the liver of homologous rats and treated with sirolimus, a m TOR inhibitor, for 4 weeks. The tumor growth was monitored by magnetic resonance imaging (MRI). The anti-angiogenesis and anti-cancer effects of sirolimus were evaluated in vivo and in vitro by microvascular density and vascular casting, cell proliferation, microtubule formation and aortic ring analysis. Results the survival time of sirolimus group was significantly longer than that of control group, tumor size was small, liver cell metastasis and ascites were less. Sirolimus also reduces intratumoral microvessel density and causes extensive necrosis of the tumor. The concentration of sirolimus required for inhibition of endothelial cell proliferation was significantly lower than that of hepatoma cell. M TOR inhibitor significantly inhibited microtubule formation and angiogenesis of arterial rings. In tumors treated with sirolimus, angiogenesis is reduced, but suppressive angiogenesis occurs. Conclusion the m TOR inhibitor can inhibit the growth of hepatoma cells and prolong the survival time of tumor-bearing rats by anti angiogenesis. The inhibitor of m TOR has the potential to treat HCC.
【作者单位】：南京中医药大学无锡附属医院;中南大学湘雅医院卫生部纳米生物技术重点实验室;
【分类号】：R735.7

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