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。
Objective To investigate the antitumoral effect of mTOR inhibitor on a HCC model. Methods Hepatoma cells were implanted into livers of syngeneic rats. The rats were treated with the mTOR inhibitor Sirolimus for 4 weeks. Tumor growth was monitored by MR imaging. Antiangiogenie effects were assessed in vivo by mierovessel density and corrosion casts and in vivo by cell proliferation, tube formation and aortic ring assays. Results The Sirolimus-treated rats had significantly longer survival time, smaller tumors, fewer extrahepatic metastases and less aseites than the controls. Sirolimus decreased intratumoral mic rovessel density resulting in extensive tumor necrosis. The Sirolimus concentration for inhibition of endothelial cell proliferation was lower than that for hepatoma cell inhibition. Microtubule formation and vascular sprouting of aortic rings were significantly impaired by mTOR inhibitor. Vascular casts revealed that Sirolimus significantly reduced vascular formation in tumors, but intussusceptive angiogenesis was observed. Conclusions roTOR inhibitor significantly reduces HCC growth and prolongs survival time primarily via antiangiogenic effect. Inhibitors of mTOR may have potential in HCC treatment.
作者
蔡靓羽
张建楠
尹卫娟
徐敏逸
赵劲风
Liang-yu Cai Jian-nan Zhang Wei-juan Yin Min-yi Xu Jin-feng Zhao(The Affiliate Chinese d Wuxi Hospital of Traditional Chinese Medicine, Nanjing University of Traditional Medicine, Wuxi, Jiangs Chinese Ministry u 214071, China Key Laboratory of Nano-biotechnology of of Health, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China)
出处
《中国现代医学杂志》
CAS
北大核心
2017年第2期36-41,共6页
China Journal of Modern Medicine
关键词
肝癌
西罗莫司
哺乳动物雷帕霉素靶蛋白
hepatocellular carcinoma
Sirolimus
mammalian target of Rapamycin
