Effects of sorafenib and regorafenib on the expression of hypoxia-inducible factors in hepatocellular carcinoma-transplanted nude mice  

作　　者：Ganxin Wang Bai Wei Qian Ma Shu Huang Qi Wu 

机构地区：[1]Division of Oncology,Liyuan Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430077,China [2]Cancer Center,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China [3]Department of Hepatology of Integrated Traditional Chinese and Western Medicine,The Third People's Hospital of Hubei Province Affiliated to Jianghan University,Wuhan 430056,China

出　　处：《Oncology and Translational Medicine》2022年第5期259-263,共5页肿瘤学与转化医学（英文版）

摘　　要：Objective The objective of this study was to investigate the inhibitory effects of sorafenib and regorafenib on the growth of hepatocellular carcinoma(HCC)using a subcutaneous transplantation tumor model in nude mice and exploring the effects of sorafenib and regorafenib on the expression of hypoxia-inducible factor(HIF)-1α,HIF-2α,and HIF-1βin HCC tissues collected from HCC-transplanted nude mice.Methods HepG2 cells were inoculated intradermally into nude mice.The mice were randomly assigned to either sorafenib treatment(100 mg/kg),regorafenib treatment(20 mg/kg),or solvent control group(dimethylsulfoxide)(n=8 per group)and received once-daily treatment for 14 days.The tumor volumes were recorded every 3 days after the initiation of treatment.The expression levels of HIF-1α,HIF-1β,HIF-2α,and SART1 in the HCC tissues were examined via quantitative real-time PCR(qRT-PCR)analysis and Western blotting.Results The tumors in the sorafenib and regorafenib treatment groups grew slower and smaller than did the tumors in the solvent control group.qPCR analysis and western blotting demonstrated that the mRNA and protein expressions of HIF-1αand HIF-1βwere down-regulated.The expression of HIF-2αand SART1 was up-regulated in the sorafenib treatment group(P<0.05);meanwhile,the expression of HIF-1αand HIF-1βwas up-regulated,and that of HIF-2αand SART1 was down-regulated in the regorafenib treatment group(P<0.05).Conclusion The expression of hypoxia-associated factor is up-regulated by sorafenib and down-regulated by regorafenib,which may induce the different effects of sorafenib on the expression of HIFs.

关 键 词：SORAFENIB REGORAFENIB liver cancer hypoxia-inducible factor hypoxia-associated factor 

分 类 号：R965[医药卫生—药理学]