Oncolytic Virus Senecavirus A Inhibits Hepatocellular Carcinoma Proliferation and Growth by Inducing Cell Cycle Arrest and Apoptosis

Background and Aims:Hepatocellular carcinoma(HCC)isa highly aggressive tumor with limited treatment options andhigh mortality.Senecavirus A(SVA)has shown potential inselectively targeting tumors while sparing healthy tissues.This study aimed to investigate the effects of SVA on HCCcells in vitro and in vivo and to elucidate its mechanisms ofaction.Methods:The cell counting kit-8 assay and colonyformation assay were conducted to examine cell proliferation.Flow cytometry and nuclear staining were employed toanalyze cell cycle distribution and apoptosis occurrence.Asubcutaneous tumor xenograft HCC mouse model was createdin vivo using HepG2 cells,and Ki67 expression in thetumor tissues was assessed.The terminal deoxynucleotidyltransferase dUTP nick end labeling assay and hematoxylinand eosin staining were employed to evaluate HCC apoptosisand the toxicity of SVA on mouse organs.Results:In vitro,SVA effectively suppressed the growth of tumor cells by inducingapoptosis and cell cycle arrest.However,it did nothave a notable effect on normal hepatocytes(MIHA cells).In an in vivo setting,SVA effectively suppressed the growthof HCC in a mouse model.SVA treatment resulted in a significantdecrease in Ki67 expression and an increase in apoptosisof tumor cells.No notable histopathological alterationswere observed in the organs of mice during SVA administration.Conclusions:SVA inhibits the growth of HCC cells byinducing cell cycle arrest and apoptosis.It does not causeany noticeable toxicity to vital organs.