Blocking CXCR3B Expression Increases Tumor Aggressiveness in Hepatocellular Carcinoma

Abstract

Background/Aim: CXCR3B has been positively involved in the inhibition of cancer and angiogenesis. The present study investigated the role of CXCR3B in a cell model of hepatocellular carcinoma, SK-Hep1. Materials and Methods: The blockade of CXCR3B expression in SK-Hep1 was investigated in terms of cell viability, cell cycle, and cell apoptosis using MTT assay and flow cytometry. In addition, the effect of blocking CXCR3B expression on cell migration and invasion was examined using scratch motility, transwell migration, and invasion assays. Furthermore, the cytotoxic effect of NK-92 cells against CXCR3B blocked SK-Hep1 was analyzed using the CytoTox96 assay, and the expression of NKp30⁺, NKG2D⁺, and NKG2C⁺ on NK-92 cells in a co-culture with SK-Hep1 was measured using flow cytometry. Results: Blocking CXCR3B expression had no effect on the viability, cell cycle or apoptosis of SK-Hep1 cells. However, blockade of CXCR3B expression significantly increased the migratory and invasive ability of SK-Hep1 along with increased protein expression of slug, vimentin, and N-cadherin. CXCR3B blockade reduced the cytotoxicity of NK-92 against SK-Hep1 and inhibited the expression of activating receptors, NKp30⁺, NKG2D⁺, and NKG2C⁺ in NK-92 cells. Conclusion: CXCR3B may play a positive role in suppressing HCC by attenuating natural killer cell cytotoxicity against HCC.