The combination of midkine inhibitor with Lenvatinib amplifies the suppression of hepatocellular carcinoma

IF 3.7 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
IUBMB Life Pub Date : 2025-05-05 DOI:10.1002/iub.70014
Xue Chen, Shujun Guo, Qilin Meng, Junye Xie, Yujie Xiao, Yuanmeng Sun, Jinchi Yao, Xinyi Jiang, An Hong, Xiaojia Chen
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引用次数: 0

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.

midkine抑制剂联合Lenvatinib可增强对肝细胞癌的抑制作用
肝细胞癌(HCC)占全球原发性肝癌病例的75%-85%。HCC患者由于肿瘤转移和耐药,预后较差;因此,需要新的治疗靶点和技术。通过Kaplan-Meier绘图数据库,我们确定了midkine (MDK)与HCC死亡率之间的强烈关联,并验证了其在许多HCC细胞系中的高表达。在体外实验中,MDK的下调降低了HCC细胞的生长和巨噬细胞的m2型极化,而MDK因子的存在导致了这些过程的增加。联合一线HCC化疗药物Lenvatinib、斑马鱼实验表明,抑制剂iMDK抑制节段间血管和肠下血管的生长,同时也减轻了心包水肿的副作用。在小鼠皮下模型中,iMDK联合Lenvatinib抑制HCC生长、血管生成和m2型巨噬细胞浸润。这些结果表明MDK是HCC的一个有希望的治疗靶点。此外,iMDK联合Lenvatinib可增强HCC抑制,从而提供了一种新的治疗选择。
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来源期刊
IUBMB Life
IUBMB Life 生物-生化与分子生物学
CiteScore
10.60
自引率
0.00%
发文量
109
审稿时长
4-8 weeks
期刊介绍: IUBMB Life is the flagship journal of the International Union of Biochemistry and Molecular Biology and is devoted to the rapid publication of the most novel and significant original research articles, reviews, and hypotheses in the broadly defined fields of biochemistry, molecular biology, cell biology, and molecular medicine.
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