Pristimerin exerts antitumor activity against MDA-MB-231 triple-negative breast cancer cells by reversing of epithelial-mesenchymal transition via downregulation of integrin β3

Background: Pristimerin, a natural flavonoid compound, has potential anti-tumor activities. These activities have been illustrated in various cancer cell lines, including MDA-MB-231 cells. MDA-MB-231 cells are a representative mesenchymal subtype of triple negative breast cancer (MES-TNBC) cell line. Currently, the main treatment for patients with advanced MES-TNBC is cytotoxic chemotherapy. We tried to examine the role and effect of pristimerin on epithelial-mesenchymal transition (EMT) in MDA-MB-231 cells. Methods: The effects of pristimerin on the proliferation of MDA-MB-231 cells were investigated by cloning formation growth assay. In vitro transwell and adhesion assays were performed for cell invasion and adhesion. The expression levels of EMT markers in E-cadherin and N-cadherin were examined by western blotting. We also established overexpressed- and silenced-integrin beta 3 cell lines to evaluate the role of integrin beta 3 in mediating the EMT reversion events in MDA-MB-231 cells. Results: Pristimerin inhibited cell proliferation, and its inhibitory effect was dose-dependent. We demonstrated that pristimerin reserved EMT by upregulating E-cadherin and downregulating N-cadherin expression. Meanwhile, we revealed that pristimerin inhibited mRNA and protein expression of integrin beta 3, which is a key heterodimeric transmembrane receptor associated with EMT. These inhibitory effects and reversion of EMT were enhanced when integrin beta 3 was knockdown in MDA-MB-231 cells, while the overexpression of integrin overexpression of integrin beta 3 attenuated these effects. In vivo studies using xenograft3 attenuated these effects. In vivo studies using xenograft mouse model demonstrated that pristimerin inhibited tumor growth. Conclusions: Our findings provide important insights into the effects of pristimerin on inhibiting cancer progression and EMT reversion by suppression of integrin beta 3.

Automated summary

The study demonstrated that pristimerin inhibits tumor growth and reverts EMT by suppressing integrin beta 3, providing important insights into its potential anti-cancer effects.