Establishment and characterization of mouse metabolic dysfunction-associated steatohepatitis-related hepatocellular carcinoma organoids

被引:0
作者
Kim, Sumin [1 ,2 ]
Jeong, Nahyun [1 ,2 ]
Park, Jeayeon [3 ,4 ]
Noh, Hyojin [3 ,4 ]
Lee, Ja Oh [1 ,2 ]
Yu, Su Jong [3 ,4 ]
Ku, Ja-Lok [1 ,2 ,5 ,6 ]
机构
[1] Seoul Natl Univ, Canc Res Inst, Coll Med, Korean Cell Line Bank,Lab Cell Biol, Seoul 03080, South Korea
[2] Seoul Natl Univ, Canc Res Inst, Seoul 03080, South Korea
[3] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 03080, South Korea
[4] Seoul Natl Univ, Liver Res Inst, Coll Med, Seoul 03080, South Korea
[5] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul 03080, South Korea
[6] Seoul Natl Univ, Ischem Hypox Dis Inst, Coll Med, Seoul 03080, South Korea
来源
SCIENTIFIC REPORTS | 2024年 / 14卷 / 01期
基金
新加坡国家研究基金会;
关键词
Hepatocellular carcinoma (HCC); Metabolic dysfunction-associated steatohepatitis (MASH); Organoid; Lenvatinib; Multi-biotics; Choline-deficient L-amino acid-defined high-fat diet (CDAHFD); NF-KAPPA-B; THERAPEUTIC TARGET; LENVATINIB; MODEL;
D O I
10.1038/s41598-024-78963-6
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Metabolic dysfunction-associated steatohepatitis (MASH) is a form of chronic liver inflammation associated with metabolic syndrome, such as obesity and a major cause of hepatocellular carcinoma (HCC). Multi-biotics, a soymilk fermented with lactic acid bacteria, are known to alleviate obesity by lowering lipid profile. This study aimed to establish and characterize mouse organoids derived from MASH-related HCC models to evaluate drug responses, particularly focusing on Lenvatinib resistance. Organoids were developed using mouse liver tissues subjected to a choline-deficient L-amino acid-defined high-fat diet (CDAHFD) to mimic MASH-related HCC. The study evaluated the effect of multi-biotics, a fermented product, on tumor regression and drug sensitivity. While multi-biotics did not reduce tumor burden, they enhanced the response to Lenvatinib. Additionally, repeated treatment with Lenvatinib led to the development of drug-resistant organoids. Transcriptomic analysis of these resistant organoids identified key pathways related to KRAS signaling, inflammation, and epithelial-mesenchymal transition (EMT), revealing potential targets for overcoming Lenvatinib resistance. This study provides valuable insights into MASH-related HCC progression and drug resistance, offering a model for further therapeutic research.
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页数:11
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