Abstract
The rates of morbidity and mortality of hepatocellular carcinoma (HCC) have not lessened because of difficulty in treating tumor metastasis. Mongolian Saussurea involucrata (SIE) possesses various anticancer activities, including apoptosis and cell cycle arrest. However, detailed effects and molecular mechanisms of SIE on metastasis are unclear. Thus, the present study was undertaken to investigate antimetastatic effects on HCC cells as well as possible mechanisms. Effects of SIE on the growth, adhesion, migration, aggregation and invasion of the SK-Hep1 human HCC cell line were investigated. SIE inhibited cell growth of metastatic cells in dose- and time-dependent manners. Incubation of SK-Hep1 cells with 200-400 μg/mL of SIE significantly inhibited cell adhesion to gelatin-coated substrate. In the migration (wound healing) and aggregation assays, SIE treated cells showed lower levels than untreated cells. Invasion assays revealed that SIE treatment inhibited cell invasion capacity of HCC cells substantially. Quantitative real time PCR showed inhibitory effects of SIE on MMP-2/-9 and MT1-MMP mRNA levels, and stimulatory effects on TIMP-1, an inhibitor of MMPs. The present study not only demonstrated that invasion and motility of cancer cells were inhibited by SIE, but also indicated that such effects were likely associated with the decrease in MMP-2/-9 expression of SK-Hep1 cells. From these results, it was suggested that SIE could be used as potential anti-tumor agent.
Highlights
Most patients with liver cancer die within one year after diagnosis largely because of frequent tumor metastasis (Suresh et al, 2011)
The present study demonstrated that invasion and motility of cancer cells were inhibited by Saussurea involucrata extract (SIE), and indicated that such effects were likely associated with the decrease in matrix metalloproteinases (MMPs)-2/-9 expression of SK-Hep1 cells
Adhesion of SK-Hep1 cells in the presence of SIE Since adhesion of tumor cells to endothelial cells is mediated by extracellular matrix (ECM) proteins, we investigated the adhesion of SK-Hep1 cells to gelatin coated surfaces either in the presence or absence of SIE
Summary
Most patients with liver cancer die within one year after diagnosis largely because of frequent tumor metastasis (Suresh et al, 2011). One critical characteristic of metastatic cancer cells is the ability to degrade basement membranes and extracellular matrix (ECM). This degradative process is mediated mainly by matrix metalloproteinases (MMPs). The two gelatinases MMP-9 (gelatinase B) and MMP2 (gelatinase A) plays a key role in degradation of the basement membrane mainly composed of collagen type IV and gelatin. These gelatinases are expressed in hepatocellular carcinoma cells and are associated with progression, metastatis and invasion of these tumors (Roomi et al, 2012). SK-Hep is invasive and expresses high MMP-9 expression levels (Lai et al, 2010) and gelatinase activity required for migration and invasion (Gianelli et al, 2001)
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