Abstract:

Objective  To evaluate the role of SPK1/S1P signal pathway in the apoptosis, invasiveness and multidrug resistance characteristics of the human hepatocellular carcinoma cell line BEL-FU after using the dimethyl sphingosine (DMS) to interfere the SPK1/S1P signal. Methods  Treated with different concentrations of dimethyl sphingosine (DMS) in the human hepatocellular carcinoma cell line BEL-FU, the morphologic change, apoptosis of cells, invasion of cells and expression of multidrug resistance-related protein (MRP1) were observed by microscopy, flow cytometry, transwell chamber assay and western blot respectively. Results  The apoptosis rate in every concentration group increased significantly compared with the control group(P<0.01), and there were significant differences among the concentration groups (P<0.01), in a dose-dependent manner. The number of invading cells decreased and the inhibitory rate of invasion increased significantly in the concentration groups compared with the control group, and there were significant differences among all the groups(P<0.01), in an apparent dose-dependent manner. The MRP1 expression level was significantly suppressed by DMS, and there were significant differences between concentration groups and the control group（P<0.05）. Conclusion  The SPK1/S1P signal is closely associated with the invasion and multidrug resistance of the human hepatocellular carcinoma cell line BEL-FU. The SPK1/S1P signal pathway interfered by DMS can induce the apoptosis, reduce the invasiveness and inhibit expression of MRP1 of the human hepatocellular carcinoma cell line BEL-FU.

Key words: Signal transduction; Liver neoplasms； Apoptosis; Invasion; Multidrug resistance-associated protein