Natural Oncolysis of Enterovirus 71 in Antitumor Therapy of Colorectal Cancer

肠道病毒71型的天然溶瘤作用在结直肠癌抗肿瘤治疗中的作用

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作者:Zhihui Ruan, Jiangyang Chi, Yue Kong, Chengcheng Li, Xiaolan Ruan, Xing Zhou, Yanxi Chen, Yongkui Li, Zhen Luo

Abstract

Colorectal cancer (CRC) is an intestinal malignant tumor with high morbidity and mortality worldwide. Inoperability or resistanance to radiation and chemotherapy occur in the conventional treatments against CRC. Oncolytic viruses (OVs) are one kind of virus that selectively infects and lyses cancer cells, which is considered to be a new anticancer therapy with biological and immune-based approaches. Enterovirus 71 (EV71), belonging to the enterovirus genus in the family Picornaviridae, is a single positive-stranded RNA virus. EV71 is transmitted in a fetal-oral route and infects gastrointestinal tract in infants. Here, EV71 is exploited to be a novel oncolytic virus in colorectal cancer. It is revealed that EV71 infection can selectively cause colorectal cancer cells cytotoxicity but not primary intestinal epithelial cells. Consistently, EV71 injection significantly inhibits tumor growth in nude mice xenografted colorectal cancer cells. In detail, EV71 infects colorectal cancer cells to repress the expression of Ki67 and B-cell leukemia 2 (Bcl-2) leading to the inhibition of cell proliferation, while activating the cleavage of poly-adenosine diphosphatase-ribose polymerase and Caspase-3 protein resulting in the promotion of cell apoptosis. The findings demonstrate the oncolytic feature of EV71 in CRC treatment and may provide a potential clue for clinical anticancer therapy.

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