Metastasis is the primary cause of death from breast cancer. Cell migration and invasion play important roles in neoplastic metastasis. The insulin like growth factor (IGF-1) stimulated cell migration through activation of PI3K/Akt signaling pathway. IGF-1 induces the tumorigenicity of many types of cancer cells and is critical for metastatic cell spread in estrogen receptor (ER)-negative breast cancer cells. Matrix metalloproteinase-2 (MMP-2) is a key enzyme in the degradation of extracellular matrices, and its expression has been dysregulated in breast cancer invasion and metastasis. Resveratrol exhibited potential anticarcinogenic activities in several studies. However, the inhibitory effects of resveratrol on the expression of MMP-2, migration and invasion of breast cancer cell have not been demonstrated yet. In the present study, we investigated the anti-invasive mechanism of resveratrol in human breast cancer MDA-MB 435cells. Here we showed that IGF-1 is a potent stimulant for the migration of ER-negative human breast cancer cells. Resveratrol could inhibit IGF-1 mediated cell migration of MDA-MB 435 in vitro. The inhibitory effect of resveratrol was mediated in part through the suppression of the activation of PI-3K/Akt signaling pathway. Furthermore, IGF-1 mediated expression of MMP-2 was significantly inhibited by resveratrol in concomitance with alteration of cell invasion.
99th AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA