title: Downregulation of B7-H4 in the MHCC97-H hepatocellular carcinoma cell line by arsenic trioxide.
abstract: Arsenic trioxide (As2O3; ATO), a compound which is characterized by its ability to function as a potent anticancer agent, has been investigated in a variety of carcinomas. B7‑H4, a transmembrane protein, may inhibit the function of the T cell effector, and therefore, may be useful in investigating different types of tumor therapies. However, few studies have been published previously associated with the roles of ATO and B7‑H4 in human hepatocellular carcinoma (HCC). The aim of the present study was to investigate the anti‑invasive role of ATO in HCC, to determine the effect of ATO treatment on the expression of B7‑H4 and to further assess the possible underlying mechanisms. Following treatment of the cells with 2, 4 and 8 µM ATO for 48 h, cell counting kit‑8 (CCK‑8), Transwell and western blot assays were used to determine the extent of human MHCC97‑H HCC cell proliferation, apoptosis, invasion and B7‑H4 expression, respectively. The results revealed that 1 µM ATO markedly decreased cellular proliferation, and ATO administered at concentrations of 0.1, 0.2 and 0.5 µM markedly inhibited the migration and invasion of the human MHCC97‑H HCC cell line. The expression of B7‑H4 in the treatment groups was markedly reduced. Signal transduction mediated via the Janus kinase 2/signal transducers and activators of transcription 3 pathway was inhibited upon treatment with 0.1, 0.2 and 0.5 µM ATO. Additionally, the protein expression levels of matrix metalloproteinase 2 and vascular endothelial growth factor were markedly reduced in HCC cells upon treatment with ATO. In conclusion, ATO may reduce the protein expression levels of B7‑H4 in MHCC97‑H HCC cells, and further affected HCC tumorigenesis and progression. ATO may be a putative agent for the development of therapeutic strategies against human liver cancer.
authors.affiliation: Department of Interventional Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
authors.forename: Liming
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Gao
authors.affiliation: Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
authors.forename: Shide
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Parasitology, Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
authors.forename: Weizhe
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000235:genetics; D010087:Oxides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1 / Q000235:genetics* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D001152:Arsenicals; D010087:Oxides; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human; D042461:Vascular Endothelial Growth Factor A; D053614:Janus Kinase 2; D020778:Matrix Metalloproteinase 2; D000077237:Arsenic Trioxide