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Breast cancer is the most common invasive cancer in women and the second leading cause of cancer death in women. However, it is not clear about its effective treatments. As a potential anticancer agent, grape seed procyanidins (GSPs) have been shown to inhibit the proliferation of various cancer cells in vitro and in vivo. In this study, it was shown that GSPs significantly inhibit MCF-7 cell proliferation in a concentration/time-dependent manner. The flow cytometric data clearly demonstrated that GSPs cause cell cycle arrest in the G2/M phase, followed by cell apoptosis. Moreover, it also confirmed that growth inhibition mediated by treatment with GSPs is related to the induction of apoptosis due to p53 elevation, purportedly by inhibition of the epidermal growth factor receptor (EGFR)/vascular endothelial growth factor (VEGF)/matrix metalloproteinase 9 (MMP9) pathway. Taken together, these findings suggest that GSPs inhibit MCF-7 cells proliferation and induce cell apoptosis by suppressing EGFR/VEGF/MMP9 pathway.

Rab family protein Rab5a has been implicated in cancer progression. To date, its expression pattern in human pancreatic cancer has not been investigated. This study aims to examine clinical significance, biological role, and potential mechanism of action of mRab5a in human pancreatic cancer. We analyzed Rab5a protein in cancer tissue of 111 cases of pancreatic cancer using immunohistochemistry. The results show that Rab5a overexpression correlates with high T stage, positive nodal status, and advanced TNM stage. We performed knockdown of Rab5a through transfection of Rab5a-specific siRNA in the Capan-2 cell line, which shows high endogenous expression, and of Rab5a plasmid in the CFPAC-1 cell line, which shows low endogenous expression. Rab5a knockdown inhibited cell proliferation and invasion while its overexpression promoted cell proliferation and invasion. In addition, overexpression of Rab5a induced resistance to 5-FU and gemcitabine while its knockdown reduced resistance to 5-FU and gemcitabine. Furthermore, our results show that Rab5a overexpression upregulates Wnt signaling and expression of Wnt target genes including c-myc and MMP7. Blocking Wnt signaling abolished the effects of Rab5a on Wnt targets and on cancer cell proliferation. In summary, our results show that Rab5a is overexpressed in pancreatic cancer and promotes aggressive biological behavior through regulation of the Wnt/β-catenin signaling pathway.