Abstract
BackgroundTetrandrine is a bisbenzylisoquinoline alkaloid isolated from the Chinese medicinal herb Stephania tetrandra S. Moore. We previously demonstrated that tetrandrine exhibits potent antitumor effects in many types of cancer cells. In this study, we investigated the effects of tetrandrine on human hepatocellular carcinoma (HCC) metastasis.MethodsThe invasion and migration effects were evaluated via wound healing and transwell assays. Immunofluorescence and western blotting analyses were used to investigate the levels of epithelial-mesenchymal transition (EMT)-related protein. A metastasis model was established to investigate the inhibitory effect of tetrandrine on hepatocellular carcinoma metastasis in vivo.ResultsTetrandrine inhibits HCC invasion and migration by preventing cell EMT. The underlying mechanism was closely associated with tetrandrine-induced human liver cell autophagy, which inhibits Wnt/β-catenin pathway activity and decreases metastatic tumor antigen 1 (MTA1) expression to modulate cancer cell metastasis.ConclusionOur findings demonstrate, for the first time, that tetrandrine plays a significant role in the inhibition of human hepatocellular carcinoma metastasis and provide novel insights into the application of tetrandrine in clinical HCC treatment.
Highlights
Tetrandrine is a bisbenzylisoquinoline alkaloid isolated from the Chinese medicinal herb Stephania tetrandra S
The results indicated that tetrandrine has the capacity to inhibit human liver cancer cell metastasis by preventing the epithelial-mesenchymal transition (EMT)
Tetrandrine inhibits hepatocellular carcinoma (HCC) cell invasion and migration To evaluate the effects of tetrandrine on HCC cells, Huh7, HCCLM9 and Hep3B cells were treated with 0 (DMSO), 0.5, 1, 2 or 4 μM of tetrandrine for 24 h
Summary
Tetrandrine is a bisbenzylisoquinoline alkaloid isolated from the Chinese medicinal herb Stephania tetrandra S. We investigated the effects of tetrandrine on human hepatocellular carcinoma (HCC) metastasis. Hepatocellular carcinoma (HCC) is one of the most common malignancies and results in approximately 600,000 deaths per year worldwide [1]. Effective treatments, such as surgical resection, liver transplantation and percutaneous ablation, may be applied at earlier stages, the very poor prognosis and high recurrence of HCC after surgical resection result in a 5-year survival rate of less than 25% [2]. With the common side effects of hand-foot skin reaction and diarrhea, sorafenib effectively controls primary tumor growth in early-stage HCC; it does not inhibit the development of secondary liver metastases or local and distant lymph node metastasis [5]. The development of an effective treatment, including therapeutic agents, for HCC
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