Abstract: Objective:To observe the inhibitory effect of tanshinone ⅡA (Tan ⅡA) on the proliferation of liver cancer HepG2 cells and its inductive effect on the migration and apoptosis of HepG2 cells, and to explore the possible mechanism. Methods:The human liver cancer HepG2 cells were cultured in vitro. The HepG2 cells were divided into blank group and different concentrations of Tan ⅡA groups. The cells in different concentrations of Tan ⅡA groups were added with Tan ⅡA at the final concentrations of 0.5, 1.0, 2.0, 5.0 and 10.0 mg·L^-1 Tan ⅡA and cultured for 24 h.The morphology of HepG2 cells in various groups was observed under inverted microscope. The inhibitory rates of proliferation of HepG2 cells in various groups were detected by MTT assay. The migration of HepG2 cells in various groups were evaluated by cell scratch assay. The expression levels of nuclear factor-κB (NF-κB) and matrix metalloproteinase-9 (MMP-9) mRNA were detected by RT-PCR method. Flow cytometry was used to detect the percentages of HepG2 cells at different cell cycles in various groups,and the apoptotic rates of HepG2 cells in various groups were detected by TUNEL method. Results:The morphology of HepG2 cells in different concentrations of Tan ⅡA groups were changed. Compared with blank group, the cells in 1.0 and 2.0 Tan ⅡA groups showed shrinkage,scattered connection and poor growth,and the inhibitory rates of proliferation of HepG2 cells in 1.0, 2.0, 5.0, and 10.0 mg·L^-1 Tan ⅡA groups were significantly increased (P<0.05) in a dose-dependent manner.The cell scratch assay results showed that with the increasing of Tan ⅡA concentration, the migration number of the cells in 2.0 and 5.0 mg·L^-1 Tan ⅡA groups were decreased significantly. Compared with 0.5 mg·L^-1 TanⅡA group, the expression levels of MMP-9 and NF-κB mRNA in the HepG2 cells in 1.0,2.0,and 5.0 mg·L^-1 Tan ⅡA groups were decresed(P<0.05 or P<0.01). The flow cytometry results showed that compared with blank group, the percentages of HepG2 cells in S phase in 1.0,2.0,5.0, and 10.0 mg·L^-1 Tan ⅡA groups were decreased (P<0.05),and the percentages of HepG2 cells in G₀/G₁ and G₂ phases were increased(P<0.05); the TUNEL results showed that compared with blank group, the apoptotic rates of HepG2 cells in 0.5, 1.0, 2.0, 5.0, and 10.0 mg·L^-1 Tan ⅡA groups werer increased (P<0.05 or P<0.01). Conclusion:Different concentrations of Tan ⅡA could significantly inhibit the proliferation and migration of human liver cancer HepG2 cells, and induce the apoptosis in a dose-dependent manner; its mechnasim may be related to the inhibition of the expressions of NF-κB and MMP-9 mRNA.

Key words: tanshinone ⅡA, liver neoplasms, cell migration, apoptosis, nuclear factor-κB, matrix metalloproteinase-9