Curcumin inhibits gastric cancer-derived mesenchymal stem cells mediated angiogenesis by regulating NF-κB/VEGF signaling.

Cancer-derived mesenchymal stem cells (MSCs) seem to play an important role in mediating tumor angiogenesis. Recently, curcumin has been shown to display multiple therapeutic properties, including anticancer activity. In the present study, we have tried to explore the role of curcumin in regulating gastric cancer cells-derived mesenchymal stem cells (GC-MSCs) mediated angiogenesis. Our results showed that curcumin attenuated the high expression levels of fibroblast proteins (α-SMA & Vimentin) in GC-MSCs. Its treatment also inhibited GC-MSCs induced human umbilical vein endothelial cells (HUVEC) tube formation, migration and colony formation. Furthermore, it was noticed that curcumin abrogated NF-κB signaling activity and VEGF production in GC-MSCs. Next, to establish the link between regulation of NF-κB/VEGF signaling by curcumin, and its influence on GC-MSC-derived angiogenesis, we pretreated GC-MSCs with either NF-κB inhibitor PDTC or a neutralizing antibody against VEGF (NA-VEGF), and then collected conditioned media (CM). The HUVEC cells were then cultured in this conditioned media to test their ability to form tubes, migrate and form colonies. Our results demonstrated that NF-κB/VEGF signaling is important for GC-MSCs induced tube formation, migration and colony formation in HUVEC cells. Moreover, we also observed that NF-κB/VEGF signaling regulated VEGF expression of gastric cancer cells both in vitro and in vivo. Overall, our study indicated that curcumin may serve as a novel therapeutic target for GC-MSCs derived angiogenesis, by inhibiting NF-κB/VEGF signaling.