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Vaccinia virus expressing IL‐37 promotes antitumor immune responses in hepatocellular carcinoma
Author(s) -
Zhang Zhihao,
Zhang Jingwen,
Zhang Yingying,
Xing Jiyuan,
Yu Zujiang
Publication year - 2019
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.3438
Subject(s) - biology , vaccinia , hepatocellular carcinoma , western blot , stat3 , cell growth , cancer research , cell culture , immune system , virology , microbiology and biotechnology , transfection , virus , immunology , phosphorylation , gene , biochemistry , genetics , recombinant dna
The aim of this study was to investigate the effect of vaccinia virus expressing IL‐37 (VV‐IL‐37) on cell proliferation, migration and invasion of hepatocellular carcinoma (HCC) and its possible underlying molecular mechanisms. In this study, we constructed a cancer‐targeted vaccinia virus carrying the IL‐37 gene knocked in the region of the viral thymidine kinase (TK) gene. Human HCC cell lines were assayed in vitro for cell proliferation, migration and invasion. Serum level, relative mRNA level and protein level of IL‐37 in HCC cell lines SMMC7721 and Bel7402 were tested by ELISA assay, qRT‐PCR and western blot, respectively. The levels of IL‐2, IFN‐γ and TNF‐α in HCC tumor tissues were also analyzed by ELISA. STAT3 and p‐STAT3 expression in tumor tissues were determined by western blot. Our results showed that VV‐IL‐37 efficiently infected and inhibited HCC cells proliferation, migration and invasion via decreasing STAT3 phosphorylation. In vivo , VV‐IL‐37 expressed IL‐37 at a high level in the transplanted tumor, reduced STAT3 activity, and eventually inhibited tumor growth. In conclusion, we demonstrate that VV‐IL‐37 promotes antitumor immune responses in HCC.