| Item type |
文献 / Documents(1) |
| 公開日 |
2023-11-09 |
| アクセス権 |
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|
アクセス権 |
open access |
| 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 |
| 出版社版DOI |
|
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|
関連識別子 |
https://doi.org/10.3390/cells12040612 |
|
|
関連名称 |
10.3390/cells12040612 |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
|
|
タイトル |
Curcumin-Mediated Resistance to Lenvatinib via EGFR Signaling Pathway in Hepatocellular Carcinoma |
| 著者 |
宮崎, 克己
森根, 裕二
Xu, Caiming
ナカス, チハル
和田, 佑馬
寺奥, 大貴
山田, 眞一郎
齋藤, 裕
池本, 哲也
島田, 光生
Goel, Ajay
|
| 抄録 |
|
|
内容記述 |
Lenvatinib is a multi-kinase inhibitor approved as a first-line treatment for patients with unresectable advanced hepatocellular carcinoma (HCC). However, its response rate is unsatisfactory, primarily due to the acquisition of resistance, which limits its clinical significance for treating patients with HCC. Recent evidence suggests that epidermal growth factor receptor (EGFR) activation can trigger Lenvatinib-resistance; and is considered an important therapeutic target in HCC. Curcumin, one of the most studied naturally occurring botanicals with robust anti-cancer activity, is also reported to be a potent tyrosine kinase inhibitor. In this study, we hypothesized that the anti-EGFR potential of Curcumin might help overcome Lenvatinib-resistance in HCC. We established two Lenvatinib-resistant cells and discovered that a combination of Curcumin and Lenvatinib exhibited a synergistic anti-tumor efficacy in the resistant HCC cell lines. In line with previous reports, Lenvatinib-resistant cell lines revealed significant activation of the EGFR, and genomewide transcriptomic profiling analysis identified that the PI3K-AKT pathway was associated with Lenvatinib resistance. The combination treatment with Curcumin and Lenvatinib dramatically suppressed gene and protein expression of the EGFR-PI3K-AKT pathway, suggesting Curcumin overcomes Lenvatinib resistance via inhibition of EGFR. We further validated these findings in tumor spheroids derived from resistant cell lines. In conclusion, we, for the first time, report that Curcumin reverses Lenvatinib resistance in HCC, and that their combination has clinical application potential for adjunctive treatment in HCC. |
| キーワード |
|
|
主題 |
Lenvatinib |
| キーワード |
|
|
主題 |
Curcumin |
| キーワード |
|
|
主題 |
EGFR |
| キーワード |
|
|
主題 |
hepatocellular carcinoma |
| キーワード |
|
|
主題 |
PI3K-AKT |
| キーワード |
|
|
主題 |
resistance |
| 書誌情報 |
en : Cells
巻 12,
号 4,
p. 612,
発行日 2023-02-14
|
| 収録物ID |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
20734409 |
| 出版者 |
|
|
出版者 |
MDPI |
| 権利情報 |
|
|
権利情報 |
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
| EID |
|
|
識別子 |
396286 |
| 言語 |
|
|
言語 |
eng |
cells_12_4_612.pdf (3.07 MB)
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