PUBLICATION
The combination of midkine inhibitor with Lenvatinib amplifies the suppression of hepatocellular carcinoma
- Authors
- Chen, X., Guo, S., Meng, Q., Xie, J., Xiao, Y., Sun, Y., Yao, J., Jiang, X., Hong, A., Chen, X.
- ID
- ZDB-PUB-250505-5
- Date
- 2025
- Source
- IUBMB life 77: e70014e70014 (Journal)
- Registered Authors
- Keywords
- Lenvatinib, combination, hepatocellular carcinoma, midkine inhibitor, therapeutic target
- MeSH Terms
-
- Animals
- Liver Neoplasms*/drug therapy
- Liver Neoplasms*/genetics
- Liver Neoplasms*/metabolism
- Liver Neoplasms*/pathology
- Carcinoma, Hepatocellular*/drug therapy
- Carcinoma, Hepatocellular*/genetics
- Carcinoma, Hepatocellular*/metabolism
- Carcinoma, Hepatocellular*/pathology
- Antineoplastic Combined Chemotherapy Protocols*/pharmacology
- Gene Expression Regulation, Neoplastic/drug effects
- Neovascularization, Pathologic/drug therapy
- Neovascularization, Pathologic/pathology
- Quinolines*/administration & dosage
- Quinolines*/pharmacology
- Phenylurea Compounds*/administration & dosage
- Phenylurea Compounds*/pharmacology
- Zebrafish
- Mice, Nude
- Xenograft Model Antitumor Assays
- Mice
- Macrophages/drug effects
- Midkine*/antagonists & inhibitors
- Midkine*/genetics
- Midkine*/metabolism
- Humans
- Cell Proliferation/drug effects
- Cell Line, Tumor
- PubMed
- 40321061 Full text @ IUBMB Life
Citation
Chen, X., Guo, S., Meng, Q., Xie, J., Xiao, Y., Sun, Y., Yao, J., Jiang, X., Hong, A., Chen, X. (2025) The combination of midkine inhibitor with Lenvatinib amplifies the suppression of hepatocellular carcinoma. IUBMB life. 77:e70014e70014.
Abstract
Hepatocellular carcinoma (HCC) accounts for 75%-85% of primary liver cancer cases globally. HCC patients have a poor prognosis because of tumor metastasis and medication resistance; thus, novel therapy targets and techniques are needed. By using the Kaplan-Meier plotter database, we identified a strong association between midkine (MDK) and HCC mortality and validated its high expression in numerous HCC cell lines. In vitro, MDK down-regulation decreased HCC cell growth and macrophage M2-type polarization, whereas the presence of the MDK factor led to an increase in these processes. Combined with the first-line chemotherapeutic agent for HCC, Lenvatinib, zebrafish experiments showed that the inhibitor iMDK inhibited the growth of intersegmental vessels and subintestinal vessels, while also mitigating the pericardial edema side effect. In a subcutaneous mouse model, the combination of iMDK with Lenvatinib inhibited HCC growth, angiogenesis, and M2-type macrophage infiltration. These results indicate that MDK represents a promising therapeutic target for HCC. Furthermore, the combination of iMDK with Lenvatinib enhances HCC inhibition, thereby presenting a novel therapy option.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping