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

J Tradit Chin Med. 2012 Sep;32(3):415-22. doi: 10.1016/s0254-6272(13)60048-5.

Abstract

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 < or = 0.001) than in controls or the SSd group (16.5%, P < or = 0.001). The model group had more intense MMP-2+ staining than controls (0.37 vs 0.27, P< or =0.01) or the SSd group (0.31 vs 0.37, P< or =0.05); and higher MMP-13+ staining (72.55%) than in controls (12.55%, P< or =0.001) and SSd group (20.18%, P< or =0.01). The model group also had more TIMP-2+ staining (57.2%) than controls (20.9%, P< or =0.001) and SSd group (22.7%, P< or=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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Drugs, Chinese Herbal / administration & dosage*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Male
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism*
  • Oleanolic Acid / administration & dosage
  • Oleanolic Acid / analogs & derivatives*
  • Rats
  • Rats, Sprague-Dawley
  • Saponins / administration & dosage*
  • Syndecan-2 / genetics
  • Syndecan-2 / metabolism*
  • Tissue Inhibitor of Metalloproteinase-2 / genetics
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism*

Substances

  • Drugs, Chinese Herbal
  • Saponins
  • Tissue Inhibitor of Metalloproteinase-2
  • Syndecan-2
  • Oleanolic Acid
  • Matrix Metalloproteinases
  • saikosaponin D