Magnesium demethylcantharidate inhibits hepatocellular carcinoma cell invasion and metastasis via activation transcription factor FOXO1.

Abstract

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.