Effects of Saikosaponin-D on syndecan-2, matrix metalloproteinases and tissue inhibitor of metalloproteinases-2 in rats with hepatocellular carcinoma

ObjectiveTo investigate effects of Saikosaponin D (SSd) on syndecan-2, matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases-2 (TIMP-2) in livers of rat with hepatocellular carcinoma (HCC).MethodsMale SD rats were divided into control (n=10), model (n=20) and SSd (n=20) groups, and model and SSd groups given intragastric 0.2% (w/v) N-diethylnitrosamine to induce HCC. SSd group received 0.03% (w/v) SSd in saline. Liver samples were analysed immunohistochemically for syndecan-2, MMP-2, MMP-13 and TIMP-2 at 16 weeks.ResultsThe model group had more malignant nodules than the SSd group; all model-group HCC cells were grade III; SSd-group HCC cells were grades I-II. Controls showed normal hepatic cell phenotypes and no syndecan-2 + staining. Syndecan-2 + staining was greater in the model group (35.2%, P≤0.001) than in controls or the SSd group (16.5%, P ≤ 0.001). The model group had more intense MMP-2 + staining than controls (0.37 vs 0.27, P≤0.01) or the SSd group (0.31 vs 0.37, P≤0.05); and higher MMP-13+ staining (72.55%) than in controls (12.55%, P≤0.001) and SSd group (20.18%, P≤0.01). The model group also had more TIMP-2 + staining (57.2%) than controls (20.9%, P≤0.001) and SSd group (22.7%, P≤0.001). Controls and SSd group showed no difference in TIMP-2+ rates.ConclusionSSd inhibited HCC development, and downregulated expression of syndecan-2, MMP-2, MMP-13 and TIMP-2 in rat HCC liver tissue.