Author:
Zhang Yejia,Xu Tian,Tian Huizhen,Wu Jianfeng,Yu Xiaomin,Zeng Lingbing,Liu Fadi,Liu Qiong,Huang Xiaotian
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.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Jiangxi Province
Training Plan for Academic and Technical Leaders of Major Disciplines in Jiangxi Province-Youth Talent Project
National Innovation and Entrepreneurship Training Program for college students
Reference42 articles.
1. Pączek, S., Łukaszewicz-Zając, M., and Mroczko, B. (2022). Granzymes—Their Role in Colorectal Cancer. Int. J. Mol. Sci., 23.
2. Oncolytic Viruses: Immunotherapy Drugs for Gastrointestinal Malignant Tumors;Li;Front. Cell. Infect. Microbiol.,2022
3. Oncolytic Viruses in Cancer Treatment: A Review;Lawler;JAMA Oncol.,2017
4. Oncolytic viruses: A new class of immunotherapy drugs;Kaufman;Nat. Rev. Drug Discov.,2016
5. Vaccinia virus-mediated cancer immunotherapy: Cancer vaccines and oncolytics;Guo;J. Immunother. Cancer,2019
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