Recombinant measles virus vaccine rMV-Hu191 exerts an oncolytic effect on esophageal squamous cell carcinoma via caspase-3/GSDME-mediated pyroptosis

Oncolytic viruses have recently been proven to be an effective and promising cancer therapeutic strategy, but there is rare data about oncolytic therapy in esophageal squamous cell carcinoma (ESCC), especially oncolytic measles virotherapy. Therefore, this study aimed to explore whether the recombin...

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Published in:Cell death discovery 2023-05, Vol.9 (1), p.171-171, Article 171
Main Authors: Wu, Ailing, Li, Zhongyue, Wang, Yilong, Chen, Yi, Peng, Jinkai, Zhu, Mengying, Li, Yueyue, Song, Hai, Zhou, Dongming, Zhang, Chudi, Lv, Yao, Zhao, Zhengyan
Format: Article
Language:English
Subjects:
631/67/1504
631/80/86
Antitumor activity
Apoptosis
Biochemistry
Biomedical and Life Sciences
Caspase-3
Cell Biology
Cell Cycle Analysis
Esophageal cancer
Inflammation
Life Sciences
Measles
Mitochondria
Oncolysis
Pyroptosis
Squamous cell carcinoma
Stem Cells
Vaccines
Viruses
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Summary:Oncolytic viruses have recently been proven to be an effective and promising cancer therapeutic strategy, but there is rare data about oncolytic therapy in esophageal squamous cell carcinoma (ESCC), especially oncolytic measles virotherapy. Therefore, this study aimed to explore whether the recombinant measles virus vaccine strain rMV-Hu191 has an oncolytic effect against ESCC cells in vitro and in vivo and elucidate the underlying mechanisms. Our results showed that rMV-Hu191 could efficiently replicate in and kill ESCC cells through caspase-3/GSDME-mediated pyroptosis. Mechanistically, rMV-Hu191 triggers mitochondrial dysfunction to induce pyroptosis, which is mediated by BAK (BCL2 antagonist/killer 1) or BAX (BCL2 associated X). Further analysis revealed that rMV-Hu191 activates inflammatory signaling in ESCC cells, which may enhance the oncolytic efficiency. Moreover, intratumoral injection of rMV-Hu191 induced dramatic tumor regression in an ESCC xenograft model. Collectively, these findings imply that rMV-Hu191 exhibits an antitumor effect through BAK/BAX-dependent caspase-3/GSDME-mediated pyroptosis and provides a potentially promising new therapy for ESCC treatment.
ISSN:2058-7716
2058-7716
DOI:10.1038/s41420-023-01466-2