Objective To explore whether emodin can inhibit the proliferation and invasion of liver cancer HepG2 cells by downregulating the expression of high mobility group box 1 (HMGB1)/receptor for advanced glycation end product (RAGE) protein.

Methods The HMGB1 overexpression plasmid (HMGB1), HMGB1 siRNA (si-HMGB1), and negative control si-NC were transfected into HepG2 cells through transient transfection, and cell migration and invasion were detected by cell scratch assay and Transwell assay; the effect of different concentrations of emodin on the proliferation in HMGB1 overexpressing HepG2 cells was detected through CCK8 assay; the expression levels of HMGB1 and RAGE proteins were analyzed by Western blotting. Based on the half maximal inhibitory concentration determined by CCK8, 4, 8, 16 μmol/L of emodin were appliied to treat HMGB1 overexpressing HepG2 cells, and the expression levels of HMGB1 and RAGE protein, as well as changes in cell migration and invasion ability were detected.

Results HMGB1 overexpressing HepG2 cells were treated with different concentrations of emodin for 24, 48, 72 h, it was found that the cell proliferation rate showed a significant downward trend with drug concentration increase (P ＜ 0.01). The results of cell scratch assay showed that after transfection with HMGB1, si-HMGB1, and si-NC for 24 h and 48 h, the migration rate of HepG2 cells in the HMGB1 group, si-NC group, and si-HMGB1 group gradually decreased (P ＜ 0.05 to P ＜ 0.01); different concentrations of emodin were used to treat HMGB1 overexpressing HepG2 cells for 24 h and 48 h, it was found that compared with the 0 μmol/L group, cell migration rate in the 4, 8, 16 μmol/L emodin groups was decreased (P ＜ 0.05). The results of Transwell assay indicated that the number of invaded and migrated HepG2 cells in the HMGB1 group, siNC group, and si-HMGB1 group gradually decreased (P ＜ 0.05); different concentrations of emodin were employed to treat HMGB1 overexpressing HepG2 cells for 24 h, it was found that compared with the 0 μmol/L group, the invaded and migrated cell numbers in the 4, 8, 16 μmol/L emodin groups were reduced (P ＜ 0.05 to P ＜ 0.01). The results of Western blotting demonstrated that the expression of HMGB1 and RAGE proteins of HepG2 cells in the HMGB1 group, si-NC group, and si-HMGB1 group gradually decreased (P ＜ 0.05); different concentrations of emodin were applied to treat HMGB1 overexpressing HepG2 cells for 24 h, it was found that compared with the 0 μmol/L group, the expression levels of HMGB1 and RAGE proteins in the 4, 8, 16 μmol/L emodin groups were reduced (P ＜ 0.05).

Conclusions Overexpression of HMGB1 significantly promotes the proliferation and invasion ability of liver cancer HepG2 cells, and emodin effectively inhibits this promoting effect by reducing the expression of HMGB1/RAGE protein.