| Ganxin Wang,Bai Wei,Qian Ma,Shu Huang,Qi Wu. Effects of sorafenib and regorafenib on the expression of hypoxia-inducible factors in hepatocellular carcinoma-transplanted nude mice. Oncol Transl Med, 2022, 8: 259-263. |
| 索拉非尼和瑞戈非尼对裸鼠移植肝细胞癌中缺氧诱导因子表达的影响 |
| Effects of sorafenib and regorafenib on the expression of hypoxia-inducible factors in hepatocellular carcinoma-transplanted nude mice |
| Received:December 25, 2021 Revised:October 10, 2022 |
| DOI：10.1007/s10330-021-0546-6 |
| 中文关键词: 索拉非尼；瑞戈非尼；肝癌；缺氧诱导因子；缺氧相关因子 |
| 英文关键词: sorafenib; regorafenib; liver cancer; hypoxia-inducible factor; hypoxia-associated factor |
| 基金项目: |
| Author Name | Affiliation | E-mail | | Ganxin Wang | Division of Oncology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology | medicine_wgx@163.com | | Bai Wei | Division of Oncology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology | | | Qian Ma | Division of Oncology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology | | | Shu Huang | Division of Oncology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology | huangshu__2020@163.com | | Qi Wu | Division of Oncology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology | |
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| 中文摘要: |
| 目的：本研究旨在通过裸鼠皮下移植肿瘤模型研究索拉非尼和瑞戈非尼对肝细胞癌（HCC）生长的抑制作用，并探讨索拉非尼和瑞戈非尼对从肝细胞癌移植的裸鼠采集的肝细胞癌组织中低氧诱导因子（HIF）HIF-1α、HIF-2α和HIF-1β表达的影响。
方法：将HepG2细胞皮内接种到裸鼠身上。小鼠被随机分配到索拉非尼治疗组（100mg/kg）、瑞戈非尼治疗组（20mg/kg）和溶剂对照组（DMSO；每组8只），每天接受一次治疗，持续14天。治疗开始后每三天记录一次肿瘤体积。肝细胞癌组织中HIF-1α、HIF-1β、HIF-2α和SART1的表达水平通过实时定量PCR（qPCR）和Western blotting检查。
结果：qPCR和Western blotting分析表明，索拉非尼治疗组的HIF-1α和HIF-1β的mRNA和蛋白表达水平下调，而HIF-2α和SART1的表达上调（P < 0.05）。相反，在瑞戈非尼治疗组中，HIF-1α和HIF-1β的表达上调，HIF-2α和SART1的表达下调（P < 0.05）。
结论:低氧相关因子被索拉非尼上调，被瑞戈非尼下调，这可能诱发了索拉非尼和瑞戈非尼对低氧诱导因子表达的不同影响。 |
| 英文摘要: |
| 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-1β in 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-1α and HIF-1β were down-regulated. The expression of HIF-2α and SART1
was up-regulated in the sorafenib treatment group (P < 0.05); meanwhile, the expression of HIF-1α and
HIF-1β was up-regulated, and that of HIF-2α and 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. |
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