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

SIMPLE SUMMARY: Colon cancer is a common malignant tumor that occurs in the digestive tract of the colon. At present, the treatment of colon cancer is unsatisfactory, and its recurrence and drug resistance are common. It is important to find an effective treatment for colon cancer. In this study, we found that coxsackievirus group B3 can induce pyroptosis in colon cancer cell lines, which shows its oncolytic activity. Based on these findings, we believe that CVB3 may play an important role in the treatment of colon cancer as an oncolytic virus. 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.