Effect of Grape Seed Proanthocyanidins on Tumor Vasculogenic Mimicry in Human Triple-negative Breast Cancer Cells

Abstract

Vasculogenic mimicry (VM) refers to the unique ability of highly aggressive tumor cells to mimic the pattern ofembryonic vasculogenesis, which was associated with invasion and metastasis. The grape seed proanthocyanidins(GSPs) had attracted much attention as a potential bioactive anti-carcinogenic agent. However, GSPs regulationof VM and its possible mechanisms in a triple-negative breast cancer cells (TNBCs) remain not clear. Therefore,we examined the effect of GSPs on VM information in HCC1937 cell model. In this study, we identified the VMstructure via the three-dimensional (3D) matrix in vitro. Cell viability was measured using the CCK8 assay. Theeffects of GSPs on human triple-negative breast cancer cells (TNBCs) HCC1937 in terms of related proteinsof VM information were determined using western blot analysis. In vitro, the tubular networks were found inhighly invasive HCC1937 cells but not in the non-invasive MCF-7 cells when plated on matrigel. The number ofvascular channels was significantly reduced when cells were exposed in GSPs (100μg/ml) and GSPs (200μg/ml)groups (all p<0.001). Furthermore, we found that treatment with GSPs promoted transition of the mesenchymalstate to the epithelial state in HCC1937 cells as well as reducing the expression of Twist1 protein, a master EMTregulator.GSPs has the ability to inhibit VM information by the suppression of Twist1 protein that could berelated to the reversal of epithelial-to-mesenchymal (EMT) process. It is firstly concluded that GSPs may be anp otential anti-VM botanical agent for human TNBCs.