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Abstract
The patients diagnosed with melanoma have a bad prognosis for early regional invasion and distant metastases. Wogonin (5,7-dihydroxy-8-methoxyflavone) is one of the active components of flavonoids that extracts from Scutellariae radix. Several previous studies reported that wogonin possesses antitumor effect against leukemia, gastrointestinal cancer and breast cancer. In this study, we used melanoma cell B16-F10 to further investigate the anti-invasive and anti-migratory activity of wogonin. Our date showed that wogonin caused suppression of cell migration, adhesion, invasion and actin remodeling by inhibiting the expression of matrix metalloproteinase-2 and Rac1 in vitro. Wogonin also reduced the number of the tumor nodules on the whole surface of the lung in vivo. Furthermore, the examination of mechanism revealed that wogonin inhibited Extracellular Regulated protein Kinases and Protein Kinase B pathways, which are both medicated by Ras. Insulin-like growth factor-1-induced or tumor necrosis factor-α-induced invasion was also inhibited by wogonin. Therefore, the inhibitory mechanism of melanoma cell invasion by wogonin might be elucidated.
Highlights
IntroductionMetastatic melanoma is the most fatal one
In skin cancer, metastatic melanoma is the most fatal one
We examined the effect of wogonin on the migration of B16F10 cells grown in a six-well plate
Summary
Metastatic melanoma is the most fatal one. It is characterized by a bad prognosis for aggressive invasion and high drug resistance [1]. Invasion gives melanoma cells the ability to break out of tissue compartments and spread locally. Invasive cells can remodel cytoskeleton and structure of the extracellular matrix (ECM) to move through tissue barriers, which includes adhesion, invasion and migration of cancer cells [2]. Matrix metalloproteinases (MMPs), a family of well-characterized structural related zinc-dependent proteases, plays a crucial role in ECM degradation [4,5]. Broad spectrum MMP inhibitors showed weak potential in tumor therapy, MMPs as key markers for prognosis and regulatory factor accord with the clinical standpoint as for melanoma
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