Investigation of Molecular Mechanisms of Tanshinone IIA on Angiogenesis and Metastasis Both in vitro and in vivo

Danshen is a common herb, which was widely used in traditional Chinese medicine for clearing the heat and extinguish blood stasis. Tanshinone IIA is the main compound in Danshen. Tanshinone IIA is a derivative of phenanthrene-quinone. It has antioxidant, antibacterial, anti-inflammatory, anti-immunological, anti-allergic, and anti-tumor properties. Tanshinone IIA exerts anti-tumor effect through inducing differentiation and apoptosis. Angiogenesis, the formation of new blood vessels to offer nutrition and oxygen is known to play an important role in tumor development and cancer cells migration to distal metastasis. However, there is none reported that tanshinone IIA exerts anticancer effect through angiogenesis pathway except cryptotanshinone. In our preliminary data, we found that tanshinone IIA could inhibit tube formation and suppressed migration with matrigel invasive assay. Therefore, we try to establish the in-vitro and in vivo model to elucidate the inhibitory effect of angiogenesis by addition with tanshinone IIA. Besides, we try to further approach the relevant mechanism associated with angiogenesis by tanshinone IIA. In our knowledge, tumor cells produce angiogenic factors including basic fibroblast growth factors (bFGF), vascular endothelial growth factors (VEGF) and platelet-derived growth factor (PDGF) to promote growth of the tumor. Cancer progression is a multi-step process in which some adhesion molecules play a pivotal role in the development of recurrent, invasive and distant metastasis. Several cell adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1, CD54), vascular cell adhesion molecule-1 (VCAM-1, CD106) and endothelial leukocyte adhesion molecule-1 (E-selectin, CD62E), have been implicated in cancer growth and metastasis. Meanwhile, inhibition of the early degradation of extracellular matrix predominantly by MMPs is considered an important strategy for antiangiogenesis. The MMP-2 and MMP-9 have been considered as enzymes in degradation of the stroma and extracellular basement proteins to allow further differentiation and spread of endothelial cells during angiogenesis. Therefore, this study aims to investigate the anti-tumor effect with the treatment of tanshinone IIA related to angiogenesis pathways and relevant mechanisms using in vivo and in vitro study. Meanwhile, we further explore the potential molecular mechanism underlying the anti-angiogenic effect of tanshinone IIA, focused particularly on the role of adhesion molecules, intracellular pathways involved and relationship with MMPs and angiogenesis.

Project ID:PC9907-2002
External Project ID:NSC99-2320-B182-014