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溶瘤麻疹病毒与熊果酸联合协同诱导肝癌细胞溶解。

Combination of Oncolytic Measles Virus and Ursolic Acid Synergistically Induces Oncolysis of Hepatocellular Carcinoma Cells.

机构信息

Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.

Department of Microbiology & Immunology, Dalhousie University, Halifax, NS B3H 4R2, Canada.

出版信息

Viruses. 2023 May 31;15(6):1294. doi: 10.3390/v15061294.

DOI:10.3390/v15061294
PMID:37376594
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10302104/
Abstract

Hepatocellular carcinoma (HCC) remains a difficult-to-treat cancer due to late diagnosis and limited curative treatment options. Developing more effective therapeutic strategies is essential for the management of HCC. Oncolytic virotherapy is a novel treatment modality for cancers, and its combination with small molecules merits further exploration. In this study, we combined oncolytic measles virus (MV) with the natural triterpenoid compound ursolic acid (UA) and evaluated their combination effect against HCC cells, including those harboring hepatitis B virus (HBV) or hepatitis C virus (HCV) replication. We found that the combination of MV and UA synergistically induced more cell death in Huh-7 HCC cells through enhanced apoptosis. In addition, increased oxidative stress and loss of mitochondrial potential were observed in the treated cells, indicating dysregulation of the mitochondria-dependent pathway. Similar synergistic cytotoxic effects were also found in HCC cells harboring HBV or HCV genomes. These findings underscore the potential of oncolytic MV and UA combination for further development as a treatment strategy for HCC.

摘要

肝细胞癌 (HCC) 仍然是一种难以治疗的癌症，因为诊断较晚且治疗方法有限。开发更有效的治疗策略对于 HCC 的治疗至关重要。溶瘤病毒治疗是癌症的一种新的治疗方式，其与小分子的联合值得进一步探索。在这项研究中，我们将溶瘤麻疹病毒 (MV) 与天然三萜化合物熊果酸 (UA) 联合使用，并评估了它们对 HCC 细胞的联合作用，包括那些携带乙型肝炎病毒 (HBV) 或丙型肝炎病毒 (HCV) 复制的细胞。我们发现 MV 和 UA 的联合通过增强细胞凋亡，在 Huh-7 HCC 细胞中协同诱导更多的细胞死亡。此外，在处理过的细胞中观察到氧化应激增加和线粒体膜电位丧失，表明线粒体依赖性途径失调。在携带 HBV 或 HCV 基因组的 HCC 细胞中也发现了类似的协同细胞毒性作用。这些发现强调了溶瘤 MV 和 UA 联合作为 HCC 治疗策略进一步开发的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0984/10302104/7a9fb92219e3/viruses-15-01294-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0984/10302104/1fe0239e94d1/viruses-15-01294-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0984/10302104/08949b3ed3eb/viruses-15-01294-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0984/10302104/748c00cd37c6/viruses-15-01294-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0984/10302104/d68863d81737/viruses-15-01294-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0984/10302104/a223c982e5b5/viruses-15-01294-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0984/10302104/7a9fb92219e3/viruses-15-01294-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0984/10302104/1fe0239e94d1/viruses-15-01294-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0984/10302104/08949b3ed3eb/viruses-15-01294-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0984/10302104/748c00cd37c6/viruses-15-01294-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0984/10302104/d68863d81737/viruses-15-01294-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0984/10302104/a223c982e5b5/viruses-15-01294-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0984/10302104/7a9fb92219e3/viruses-15-01294-g006.jpg

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