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

OBJECTIVE: To 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). METHODS: Male 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. RESULTS: The 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. CONCLUSION: SSd inhibited HCC development, and downregulated expression of syndecan-2, MMP-2, MMP-13 and TIMP-2 in rat HCC liver tissue. (C) 2012 JTCM. All rights reserved.