Inhibition of Dickkopf-1 enhances the anti-tumor efficacy of sorafenib via inhibition of the PI3K/Akt and Wnt/β-catenin pathways in hepatocellular carcinoma

Autor: Sang Hyun Seo, Kyung Joo Cho, Hye Jung Park, Hye Won Lee, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Jae Hee Cheon, Jong In Yook, Man-Deuk Kim, Dong Jin Joo, Seung Up Kim
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cell Communication and Signaling, Vol 21, Iss 1, Pp 1-18 (2023)
Druh dokumentu: article
ISSN: 1478-811X
DOI: 10.1186/s12964-023-01355-2
Popis: Abstract Background Sorafenib improves the overall survival in patients with advanced hepatocellular carcinoma (HCC). Dickkopf-1 (DKK1) is commonly overexpressed in HCC. In this study, we investigated whether the inhibition of DKK1 enhances the anti-tumor efficacy of sorafenib in HCC. Methods HCC cells were treated with sorafenib and WAY-262611, which is an inhibitor of DKK1. Transgenic mouse models were also developed using hydrodynamic tail vein injection. Mice were orally administered with sorafenib (32 mg/kg), WAY-262611 (16 mg/kg), or sorafenib + WAY-262611 for 10 days. Mechanisms of sorafenib and WAY-262611 were explored via western blotting, immunostaining, and RNA sequencing. Results DKK1 was significantly overexpressed in patients with HCC than in the healthy controls and patients with liver diseases except HCC (all P
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