Matrine induces cell cycle arrest and apoptosis in hepatocellular carcinoma cells via miR-122 mediated CG1/livin/survivin signal axis

Purpose: To study the impact of matrine on cell cycle and apoptotic changes in hepatoma cells, and the mechanism involved. Methods: Human hepatoma cell line HepG2 was treated with different concentrations of matrine. The blank control cells were maintained in 1640 medium only. The influence of matrine on proliferative ability was determined with 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) method. Flow cytometry was used to determine its effect on cell cycle and apoptosis; RT-PCR (reverse transcription-polymerase chain reaction) was applied to assay the mRNA expressions of miR-122, cyclin G1 (CG1), livin and survivin mRNA, while the protein expressions of CG1, livin and surviving were assayed by Western blotting. Results: Matrine time- and dose-dependently suppressed the proliferative capacity of the cells. At a concentration of 0.5 mg/mL, matrine had no significant effect on the cell cycle. However, 1.0 mg/mL matrine blocked the cell cycle in G1 phase, while 1.5 mg/mL matrine blocked HepG2 cells in G2/M phase (p < 0.05). Moreover, matrine induced apoptosis in HepG2 cells, and markedly downregulated the expressions of miR-122 concentration- time-reliantly (p < 0.05). In addition, matrine markedly and concentration-dependently reduced mRNA and protein expression levels of CG1, livin and survivin, with the strongest inhibitory effect at a level of 1.5 mg/mL. Conclusion: Matrine induces cell cycle block and apoptotic changes in hepatoma cells through a mechanism related to regulation of the CG1/livin/survivin signal axis mediated by miR-122. Matrine may be a potential treatment for liver cancer. However, clinical trials are needed to confirm this potential.