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

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.

Automated summary

Hepatocellular carcinoma (HCC) is a challenging cancer to treat and requires more effective therapeutic strategies. In this study, the combination of oncolytic measles virus (MV) and natural triterpenoid compound ursolic acid (UA) showed synergistic cytotoxic effects on HCC cells, including those with hepatitis B virus (HBV) or hepatitis C virus (HCV) replication. The combination induced enhanced apoptosis, increased oxidative stress, and dysregulation of the mitochondria-dependent pathway. These findings highlight the potential of the MV and UA combination as a treatment strategy for HCC.