1. Academic Validation
  2. Coxsackievirus Group B3 Has Oncolytic Activity against Colon Cancer through Gasdermin E-Mediated Pyroptosis

Coxsackievirus Group B3 Has Oncolytic Activity against Colon Cancer through Gasdermin E-Mediated Pyroptosis

  • Cancers (Basel). 2022 Dec 15;14(24):6206. doi: 10.3390/cancers14246206.
Yejia Zhang 1 Tian Xu 1 Huizhen Tian 1 Jianfeng Wu 1 Xiaomin Yu 1 Lingbing Zeng 1 2 Fadi Liu 3 Qiong Liu 1 Xiaotian Huang 1
Affiliations

Affiliations

  • 1 Department of Medical Microbiology, School of Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330006, China.
  • 2 Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
  • 3 The Department of Clinical Laboratory, Children's Hospital of Jiangxi Province, Nanchang 330006, China.
Abstract

Colon Cancer is the second leading cause of cancer-related death, and there are few effective therapies for colon Cancer. This study explored the use of coxsackievirus group B3 (CVB3) as an oncolytic virus for the treatment of colon Cancer. In this study, we verified that CVB3 induces death of colon Cancer cell lines by directly observing cell morphology and Western blot results, and observed the oncolytic effects of CVB3 by constructing an immunodeficient nude mice model. Our data show that CVB3 induces Pyroptosis in colon Cancer cell lines. Mechanistically, we demonstrated that CVB3 causes cleavage of gasdermin E (GSDME), but not gasdermin D (GSDMD), by activating Caspase-3. This leads to production of GSDME N-termini and the development of pores in the plasma membrane, inducing Pyroptosis of colon Cancer cell lines. We also demonstrate that CVB3-induced Pyroptosis is promoted by Reactive Oxygen Species (ROS). Finally, in vivo studies using immunodeficient nude mice revealed that intratumoral injection of CVB3 led to significant tumor regression. Our findings indicate that CVB3 has oncolytic activity in colon Cancer cell lines via GSDME-mediated Pyroptosis.

Keywords

GSDME; caspase-3; colon cancer; coxsackievirus group B3; oncolytic viruses; pyroptosis.

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