PIVKA-Ⅱ levels in HCC tissues and effect of vitamin K₂ on the expression of PIVKA-Ⅱ in HCC cells

Objective To observe the expression of Vitamin K deficiency or antagonist-Ⅱ-induced protein (PIVKA-Ⅱ) in human hepatocellular carcinoma (HCC) and the effect of vitamin K₂ on the expression of PIVKA-Ⅱ in HCC cells,to explore the relationship between PIVKA-Ⅱ and HCC and its possible mechanism. Methods One hundred pairs of primary liver cancer tissue and adjacent tissue samples of surgical resection in Zhejiang Cancer Hospital from January,2012 to December,2015 were selected.The expression of PIVKA-Ⅱ in tissues was determined by ABC immunohistochemical method.The level of PIVKA-Ⅱ in the samples was determined by electrochemiluminescence immunoassay.HepG-2 cells were co-cultured with VitK₂ at concentration of 20 μM.The effect of VitK₂ on the expression of PIVKA-Ⅱ in HepG-2 cells was determined by enzyme-linked immunosorbent assay (ELISA).MTT assay was used to determine the effect of VitK₂ on the growth of HepG-2 cells.The effect of VitK₂ on the invasive ability of HepG-2 cells was determined by Transwell method. Results The positive rate of PIVKA-Ⅱ in hepatocellular carcinoma (74.0%) was higher than that in para-cancerous tissues (25.0%),P<0.05.The level of PIVKA-Ⅱ in hepatocellular carcinoma (3 786.23±143.24) mAU/g was higher than that in para-cancerous tissues (167.34±21.54) mAU/g (P<0.05).The level of PIVKA-Ⅱ in hepatocarcinoma cells in control group was (3.43±0.04) ng/(ml·10⁶ cells),the level of PIVKA-Ⅱ in VitK₂ group was (2.57±0.02) ng/(ml·10⁶ cells).The PIVKA-Ⅱ level in VitK₂ group was significantly lower than that in control group (P<0.05).On the 1st,2nd,3rd,4th,5th and 6th day of VitK₂ was co-cultured with HepG-2 cells,the inhibitory rates of VitK₂ on HepG-2 cells were 9.2%,16.5%,26.7%,34.8%,41.2% and 46.7%,respectively.After 24 h of VitK₂ was co-cultured with HepG-2 cells,VitK₂ on HepG-2 liver cancer cell invasion inhibition rate was 37.2%. Conclusion The expression of PIVKA-Ⅱ in hepatocellular carcinoma was high.VitK₂ can reduce the level of PIVKA-Ⅱ in hepatocarcinoma cells,inhibit the growth of hepatocarcinoma cells and reduce the invasiveness of HCC cells.