Integrated multi-omics demonstrates enhanced antitumor efficacy of donafenib combined with FADS2 inhibition in hepatocellular carcinoma

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2024-11-17 DOI:10.1016/j.tranon.2024.102142

Hui Li, Yafeng Dai, Di Wu, Song Gao, Jianhai Guo, Pengjun Zhang, Hui Chen, Fuxin Kou, Shaoxing Liu, Aiwei Feng, Baojiang Liu, Dongdong Hou, Xu Zhu

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引用次数: 0

Abstract

Pharmacotherapy is crucial for advanced hepatocellular carcinoma (HCC). The multi-kinase inhibitor donafenib offers superior survival benefits over sorafenib. Donafenib has first-line status, but there is limited research for combination therapies with this anticancer agent. This study aimed to delineate donafenib's antitumor effects, including transcriptomics and proteomics to characterize gene expression changes in donafenib-treated HCC cell lines. In vitro and in vivo tumorigenicity studies were conducted to evaluate the combined antitumor effects of donafenib. Proteomic and transcriptomic analyses identified that donafenib downregulated fatty acid desaturase 2 (FADS2) at the protein and mRNA levels. In vitro and in vivo assays revealed an inhibitory effect of FADS2 blockade on HCC cell malignancy. The combination of donafenib and the FADS2 inhibitor sc-26,196 produced synergistic antitumor action, enhancing therapeutic efficacy in HCC cell lines and xenografted tumors in nude mice. These findings highlight the potential of FADS2 as a biomarker for HCC and show a promising combinatorial therapy for its treatment. Thus, we provide a theoretical basis for translating laboratory research into clinical applications.

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多组学综合研究表明，多纳非尼联合 FADS2 抑制剂可增强肝细胞癌的抗肿瘤疗效。

药物治疗对晚期肝细胞癌（HCC）至关重要。多激酶抑制剂多纳非尼的生存期优于索拉非尼。多纳非尼具有一线治疗的地位，但与这种抗癌药物联合治疗的研究却很有限。本研究旨在阐明多纳非尼的抗肿瘤作用，包括通过转录组学和蛋白质组学分析多纳非尼治疗的HCC细胞系的基因表达变化。研究还进行了体外和体内致瘤性研究，以评估多纳非尼的综合抗肿瘤作用。蛋白质组和转录组分析发现，多纳非尼在蛋白质和mRNA水平下调了脂肪酸去饱和酶2（FADS2）。体外和体内试验显示，FADS2阻断对HCC细胞恶性肿瘤有抑制作用。多奈非尼和 FADS2 抑制剂 sc-26,196 联合使用可产生协同抗肿瘤作用，提高对 HCC 细胞系和裸鼠异种移植肿瘤的疗效。这些发现凸显了 FADS2 作为 HCC 生物标记物的潜力，并展示了治疗 HCC 的组合疗法的前景。因此，我们为将实验室研究转化为临床应用提供了理论基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.