Nrf2 signaling in sorafenib-resistant HCC
Gao, Luping Tokushima University
森根, 裕二 Tokushima University 徳島大学 教育研究者総覧 KAKEN研究者をさがす
山田, 眞一郎 Tokushima University 徳島大学 教育研究者総覧 KAKEN研究者をさがす
齋藤, 裕 Tokushima University 徳島大学 教育研究者総覧 KAKEN研究者をさがす
池本, 哲也 Tokushima University 徳島大学 教育研究者総覧 KAKEN研究者をさがす
徳田, 和憲 Tokushima University
髙須, 千絵 Tokushima University 徳島大学 教育研究者総覧 KAKEN研究者をさがす
宮崎, 克己 Tokushima University
島田, 光生 Tokushima University 徳島大学 教育研究者総覧 KAKEN研究者をさがす
Background and aim
As a multiple tyrosine kinase inhibitor, sorafenib is widely used to treat hepatocellular carcinoma (HCC), but patients frequently face resistance problems. Because the mechanism controlling sorafenib-resistance is not well understood, this study focused on the connection between tumor characteristics and the Nrf2 signaling pathway in a sorafenib-resistant HCC cell line.
A sorafenib-resistant HCC cell line (Huh7) was developed by increasing the dose of sorafenib in the culture medium until the target concentration was reached. Cell morphology, migration/invasion rates, and expression of stemness-related and ATP-binding cassette (ABC) transporter genes were compared between sorafenib-resistant Huh7 cells and parental Huh7 cells. Next, a small interfering RNA was used to knock down Nrf2 expression in sorafenib-resistant Huh7 cells, after which cell viability, stemness, migration, and ABC transporter gene expression were examined again.
Proliferation, migration, and invasion rates of sorafenib-resistant Huh7 cells were significantly increased relative to the parental cells with or without sorafenib added to the medium. The expression levels of stemness markers and ABC transporter genes were up-regulated in sorafenib-resistant cells. After Nrf2 was knocked down in sorafenib-resistant cells, cell migration and invasion rates were reduced, and expression levels of stemness markers and ABC transporter genes were reduced.
Nrf2 signaling promotes cancer stemness, migration, and expression of ABC transporter genes in sorafenib-resistant HCC cells.
This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
pone_16_9_e0256755.pdf 1.69 MB