Hepatocellular carcinoma (HCC) is one of the most common malignant
tumors in the world, develops rapidly and has a high mortality rate. Relapsed
metastasis is the most important factor affecting prognosis and is also the main cause of death for patients with HCC.
Cantharidin is a kind of
folk medicine for malignant
tumors in China. Because of its cytotoxicity, the application of
cantharidin is very limited.
Magnesium demethylcantharidate (MDC) is a derivative of
cantharidin independently developed by our laboratory. Our results show that MDC has anticancer activity and exhibited lower toxicity than
cantharidin. However, whether MDC affects the invasion and
metastasis of HCC cells and the underlying molecular mechanisms remain obscure. Transwell and
Matrigel assays showed that MDC could effectively inhibit the invasion and
metastasis of the HCC cell lines SMMC-7721 and SK-Hep1 in a dose-dependent manner. Moreover, MDC significantly inhibited the expression of invasion and
metastasis related
proteins MMP-2 and MMP-9. In addition, our study found that MDC inhibited the invasion and
metastasis of HCC cell lines SMMC-7721 and SK-Hep1 by activating
transcription factor FOXO1. Interestingly, the combination of MDC and
sorafenib significantly inhibited the invasion and
metastasis of HCC cell lines SMMC-7721 and SK-Hep1 compared with the single drug treatment via the activated
transcription factor FOXO1. Our work revealed that MDC obviously inhibited the invasion and
metastasis of HCC cells, and suggested that MDC could be a potential candidate molecule against the invasion and
metastasis of HCC.