| アイテムタイプ |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2025-10-17 |
| タイトル |
|
|
タイトル |
Cabozantinib inhibits the growth of lenvatinib-resistant hepatoma cells restoring FTCD expression |
|
言語 |
en |
| 言語 |
|
|
言語 |
eng |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| アクセス権 |
|
|
アクセス権 |
open access |
|
アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 著者 |
藤田, 浩二
Yamada, Mari
森下, 朝洋
小野, 正文
樋本, 尚志
小原, 英幹
正木, 勉
|
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
Cabozantinib is a newly developed tyrosine kinase inhibitor, which is applied on patients with hepatocellular carcinoma (HCC) unresponsive to conventional tyrosine kinase inhibitors, including lenvatinib. However, the mechanism of cabozantinib efficacy for lenvatinib-resistant tumor cells has not been well established in basic studies. The purpose of this study is to elucidate the mechanisms by which cabozantinib inhibits tumor growth of lenvatinib-resistant hepatocellular carcinoma cell lines in vitro and in vivo. We established a lenvatinib-resistant Hep3B cell line (Hep3B-LR) and evaluated the inhibitory effect of cabozantinib on the growth of Hep3B-LR cells. Hep3B-LR exhibited approximately 20 times greater IC50 for lenvatinib than the wild type. Compared with wild-type Hep3B, Hep3B-LR was characterized by enhanced expression of EGFR, MET and ErbB2. Cabozantinib suppressed tumor growth of Hep3B-LR in vitro and in vivo. Microarray analysis and real-time qPCR using the xenografts revealed cabozantinib downregulated miR-126-3p, a tumor suppressor miRNA, suggesting that miR-126-3p did not contribute to tumor inhibitory effect of cabozantinib. Proteome analysis using xenograft tissues demonstrated an upregulation of FTCD, a tumor suppressor gene, by cabozantinib administration. The enhanced expression of FTCD by cabozantinib was confirmed by western blot and immunohistochemistry analysis. Furthermore, FTCD expression in Hep3B-LR before cabozantinib administration was weaker than that in wild-type Hep3B. FTCD expression was weakened along with acquisition of lenvatinib-resistance, and was restored by cabozantinib administration. FTCD may be a novel therapeutic target of cabozantinib in case of lenvatinib treatment failure. |
|
言語 |
en |
| 書誌情報 |
en : Biochemical Pharmacology
巻 226,
発行日 2024-08-01
|
| 出版者 |
|
|
出版者 |
Elsevier |
|
言語 |
en |
| ISSN |
|
|
収録物識別子タイプ |
EISSN |
|
収録物識別子 |
1873-2968 |
| 助成情報 |
|
|
|
識別子タイプ |
Crossref Funder |
|
|
助成機関識別子 |
https://doi.org/10.13039/501100001691 |
|
|
助成機関識別子タイプURI |
https://www.crossref.org/services/funder-registry/ |
|
|
助成機関名 |
日本学術振興会 |
|
|
言語 |
ja |
|
|
助成機関名 |
Japan Society for the Promotion of Science |
|
|
言語 |
en |
|
|
研究課題番号 |
22K07473 |
|
|
研究課題番号URI |
https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-22K07473/ |
|
|
研究課題名 |
肝細胞癌の抗がん剤耐性獲得機構におけるmiRNAの機能解析 |
|
|
言語 |
ja |
| PubMed番号 |
|
|
|
識別子タイプ |
PMID |
|
|
関連識別子 |
38815631 |
| 著者版フラグ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Drug resistance |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Hepatocellular carcinoma |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Multikinase inhibitors |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Proteome |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
miRNA |
BP226_116321
