Genistein, the most abundant phytoestrogen in soybeans, may bind to estrogen receptors and perform anticancer activities. Choriocarcinoma is a malignant, trophoblastic and aggressive cancer of the placenta. Few studies are currently available concerning the effects of genistein on choriocarcinoma. In the present study, we investigated the effect of genistein on the invasive potential of the choriocarcinoma cell line JAR and its underlying mechanism. Our data revealed that genistein inhibited JAR cell invasion in a dose-dependent manner by a matrigel invasion assay. Moreover, genistein was found to have decreased the metastasis-associated gene MTA3 mRNA level, increased the transcriptional suppressor Snail mRNA level and upregulated the protein expression of the cell-cell adhesion molecule E-cadherin by real-time RT-PCR and Western blot analysis, respectively. ERβ siRNA was used to knock down ERβ expression in JAR cells. In the ERβ-knockdown JAR cells, genistein failed to inhibit JAR cell invasion. The effects of genistein on MTA3, Snail and E-cadherin expression were also eradicated following ERβ siRNA transfection. These results demonstrated that genistein triggered the MTA3/Snail/E-cadherin regulatory pathway by binding with ERβ, thereby inhibiting JAR cell invasion. In conclusion, our findings have significant implications for the prevention and therapy of choriocarcinoma.

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