Inhibition of B7-H4 promotes hepatocellular carcinoma cell apoptosis and autophagy through the PI3K signaling pathway

Abstract

B7-H4 and autophagy can regulate or be induced by the PI3K signaling pathway. However, the association between B7-H4 and autophagy in hepatocellular carcinoma (HCC)remains unclear. The aim of this work was to investigate whether B7-H4 regulates autophagy via the PI3K signaling pathway in HCC cells. Here, western blotting was used to measure the expression of the related proteins involved in changes in of autophagy and apoptosis, such as LC3, P62, cleaved caspase 3, cleaved PARP, BCL-2, and BAX in Huh7 and Hep3B cells. Additionally, PI3K/AKT/mTOR signaling pathway proteins were measured. Cell counting kit-8 and flow cytometry were used to analyze the effects of B7-H4 siRNA interference on cell proliferation with the interference of B7-H4 siRNA. We found that B7-H4 siRNA increased HCC cell apoptosis and autophagy, and reduced cell proliferation. Moreover, the apoptosis-related proteins cleaved caspase 3, cleaved PARP and BAX were increased and Bcl-2 was decreased after B7-H4 siRNA interference. The expression level of the autophagy-related protein LC3Ⅱ was upregulated, while expression of the autophagy adaptor P62 expression was decreased in B7-H4 siRNA-pretreated cells. Furthermore, our data revealed that B7-H4 regulated apoptosis and autophagy through the PI3K signaling pathway in HCC cells. Therefore, these results suggested that B7-H4 plays an important role in HCC progression by affecting cell apoptosis and autophagy.