Abstract:

Objective To investigate the effects of low molecular weight heparin (LMWH) on proliferation and cell cycle distribution of human hepatocacinoma cell line SMMC-7721 cultured in vitro,  and expressions of Skp2 and c-Myc relevant to cycle regulation. Methods SMMC-7721 cells were cultured in vitro then treated by LMWH of different concentrations for different periods of time. Then the cell survival and growth were determined by MTT assay. After cells of negative control group and LMWH treated groups (400 IU/mL and 800 IU/mL) were cultured for 36 h, the cell cycle distributions were analyzed by flow cytometry; alterations of Skp2 and c-Myc mRNA were examined by RT-PCR; and expression alterations of Skp2 and c-Myc proteins were investigated by Western blotting. Results Compared to negative control group, the cell proliferation of LMWH treated groups was inhibited and presented dose-dependent and time-dependent within a certain range. The cell cycle distributions altered and with the increasing of LMWH dose, the percent of cells in S phase decreased (P<0.05) and G0/G1 phase increased (P<0.05). In addition, the mRNA and protein expressions of Skp2 and c-Myc were dose-dependently reduced (P<0.05). Conclusion LMWH can inhibit the proliferation of SMMC-7721 cells. The mechanism may be relevant to reducing the expressions of Skp2 and c-Myc and arresting cell cycle at G0/G1 phase and consequently decreasing the cell proliferation index.

Key words: low molecular weight heparin, hepatocarcinoma, proliferation, cell cycle