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Expressions of B7-H4 and B7-H3 Proteins and Effect of Sorafenib on their Expressions in Different Human Hepatoma Cell Lines
Abstract
Purpose: To study whether B7-H3 and B7-H4 proteins can be candidate drug targets for preventing and treating hepatoma.
Methods: Western blot assay was used to study the expressions of B7-H3 and B7-H4 proteins and the effect of sorafenib on their expressions in different human hepatoma cell lines (HepG2, Hep3B, BEL- 7402, BEL-7404, BEL-7405, QGY-7701, QGY-7703, SMMC-7721, MHCC97H, MHCC97L, HCCLM3 and HCCLM6). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to study the cytotoxicity of sorafenib against different human hepatoma cell lines.
Results: The expressions of B7-H3 (0.26 - 0.84 μM) and B7-H4 (0.18 - 0.78 μM) proteins in different human hepatoma cell lines were significantly (p < 0.01) up-regulated, compared with that of the normal human liver cell line (HL-7702) (0.09 and 0.08 μM). Sorafenib was cytotoxic on Hep3B, BEL-7404, MHCC97H, HCCLM3 and HCCLM6 cells with half-maximal inhibitory concentration (IC50) of 14.56, 9.14, 9.46, 17.21 and 9.29 μM, respectively. After treatment with sorafenib at concentrations of 5, 10 and 20 μM, the expressions of B7-H3 protein in MHCC97H, HCCLM3 and HCCLM6 cells and the expressions of B7-H4 protein in Hep3B, BEL-7404 and MHCC97H cells were significantly (p < 0.01) down-regulated, compared with that of the control.
Conclusion: Over-expression of B7-H3 and B7-H4 proteins is common in different human hepatoma cell lines and thus, B7-H3 and B7-H4 proteins may be regarded as candidate drug targets for preventing and treating hepatoma.
Keywords: Hepatoma, B7-H3, B7-H4, Sorafenib, Over-expression, Cytotoxic activity, Down-regulation