Downregulation of B7-H4 in the MHCC97-H hepatocellular carcinoma cell line by arsenic trioxide

Arsenic trioxide (As(2)O(3); 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.