典型文献
Rapamycin enhances the anti-tumor activity of cabozantinib in cMet inhibitor-resistant hepatocellular carcinoma
文献摘要：
Cabozantinib,mainly targeting cMet and vascular endothelial growth factor receptor 2,is the second-line treatment for patients with advanced hepatocellular carcinoma(HCC).However,the lower response rate and resistance limit its enduring clinical benefit.In this study,we found that cMet-low HCC cells showed primary resistance to cMet inhibitors,and the combination of cabozantinib and mammalian target of rapamycin(mTOR)inhibitor,rapamycin,exhibited a synergistic inhibitory effect on the in vitro cell proliferation and in vivo tumor growth of these cells.Mechanically,the combination of rapamycin with cabozantinib resulted in the remarkable inhibition of AKT,extracellular signal-regulated protein kinases,mTOR,and common downstream signal molecules of receptor tyrosine kinases;decreased cyclin D1 expression;and induced cell cycle arrest.Meanwhile,rapamycin enhanced the inhibitory effects of cabozantinib on the migration and tubule formation of human umbilical vascular endothelial cells and human growth factor-induced invasion of cMet inhibitor-resistant HCC cells under hypoxia condition.These effects were further validated in xenograft models.In conclusion,our findings uncover a potential combination therapy of cabozantinib and rapamycin to combat cabozantinib-resistant HCC.
文献关键词：
中图分类号：
作者姓名：
Chao Gao;Shenghao Wang;Weiqing Shao;Yu Zhang;Lu Lu;Huliang Jia;Kejin Zhu;Jinhong Chen;Qiongzhu Dong;Ming Lu;Wenwei Zhu;Lunxiu Qin
作者机构：
Department of General Surgery,Huashan Hospital,Cancer Metastasis Institute,Fudan University,Shanghai 200040,China;Kanion Research Institute,Lianyungang 222002,China;Institutes of Biomedical Sciences,Fudan University,Shanghai 200040,China
文献出处：
引用格式：
[1]Chao Gao;Shenghao Wang;Weiqing Shao;Yu Zhang;Lu Lu;Huliang Jia;Kejin Zhu;Jinhong Chen;Qiongzhu Dong;Ming Lu;Wenwei Zhu;Lunxiu Qin-.Rapamycin enhances the anti-tumor activity of cabozantinib in cMet inhibitor-resistant hepatocellular carcinoma)[J].医学前沿,2022(03):467-482
A类：
cabozantinib,cMet,Cabozantinib
B类：
Rapamycin,enhances,tumor,activity,resistant,hepatocellular,carcinoma,mainly,targeting,vascular,endothelial,growth,receptor,second,line,treatment,patients,advanced,HCC,However,lower,response,rate,resistance,limit,its,enduring,clinical,benefit,In,this,study,found,that,cells,showed,primary,inhibitors,combination,mammalian,rapamycin,mTOR,exhibited,synergistic,inhibitory,vitro,proliferation,vivo,these,Mechanically,resulted,remarkable,inhibition,AKT,extracellular,signal,regulated,protein,kinases,common,downstream,molecules,tyrosine,decreased,cyclin,D1,expression,induced,cycle,arrest,Meanwhile,enhanced,effects,migration,tubule,formation,human,umbilical,invasion,under,hypoxia,condition,These,were,further,validated,xenograft,models,conclusion,our,findings,uncover,potential,therapy,combat
AB值：
0.532671
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