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Regorafenib 对肝癌细胞系中 microRNA 表达的抗肿瘤作用。

Antitumor Effect of Regorafenib on MicroRNA Expression in Hepatocellular Carcinoma Cell Lines.

机构信息

Department of Gastroenterology and Neurology, Faculty of Medicine, Graduate School of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho 761-0793, Kita-gun, Kagawa, Japan.

Life Science Research Center, Kagawa University, 1750-1 Ikenobe, Miki-cho 761-0793, Kita-gun, Kagawa, Japan.

出版信息

Int J Mol Sci. 2022 Jan 31;23(3):1667. doi: 10.3390/ijms23031667.

DOI:10.3390/ijms23031667
PMID:35163589
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8835935/
Abstract

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is one of the leading causes of cancer-related deaths worldwide. Regorafenib, a multi-kinase inhibitor, is used as a second-line treatment for advanced HCC. Here, we aimed to investigate the mechanism of the antitumor effect of regorafenib on HCC and evaluate altered microRNA (miRNA) expression. Cell proliferation was examined in six HCC cell lines (HuH-7, HepG2, HLF, PLC/PRF/5, Hep3B, and Li-7) using the Cell Counting Kit-8 assay. Xenografted mouse models were used to assess the effects of regorafenib in vivo. Cell cycle analysis, western blotting analysis, and miRNA expression analysis were performed to identify the antitumor inhibitory potential of regorafenib on HCC cells. Regorafenib suppressed proliferation in HuH-7 cell and induced G0/G1 cell cycle arrest and cyclin D1 downregulation in regorafenib-sensitive cells. During miRNA analysis, miRNA molecules associated with the antitumor effect of regorafenib were found. Regorafenib suppresses cell proliferation and tumor growth in HCC by decreasing cyclin D1 via alterations in intracellular and exosomal miRNAs in HCC.

摘要

肝细胞癌（HCC）是肝脏最常见的原发性恶性肿瘤，也是全球癌症相关死亡的主要原因之一。regorafenib 是一种多激酶抑制剂，被用作晚期 HCC 的二线治疗药物。在这里，我们旨在研究 regorafenib 对 HCC 的抗肿瘤作用机制，并评估其改变的 microRNA（miRNA）表达。使用 Cell Counting Kit-8 测定法在六种 HCC 细胞系（HuH-7、HepG2、HLF、PLC/PRF/5、Hep3B 和 Li-7）中检查细胞增殖。使用异种移植小鼠模型评估 regorafenib 在体内的作用。进行细胞周期分析、western blot 分析和 miRNA 表达分析，以确定 regorafenib 对 HCC 细胞的抗肿瘤抑制潜力。regorafenib 抑制 HuH-7 细胞的增殖，并在 regorafenib 敏感细胞中诱导 G0/G1 细胞周期停滞和细胞周期蛋白 D1 下调。在 miRNA 分析中，发现了与 regorafenib 抗肿瘤作用相关的 miRNA 分子。Regorafenib 通过改变 HCC 细胞内和外泌体中的 miRNA 来降低细胞周期蛋白 D1，从而抑制 HCC 中的细胞增殖和肿瘤生长。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba82/8835935/763b1474875d/ijms-23-01667-g006.jpg
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