Ginsenoside Rd regulates the Akt/mTOR/p70S6K signaling cascade and suppresses angiogenesis and breast tumor growth

Blockade of angiogenesis is an important approach for cancer treatment and prevention. In the present study, we investigated the effect of ginsenoside Rd (Rd) on angiogenesis in vitro and in vivo. Our results demonstrated that Rd inhibited vascular endothelial growth factor (VEGF)-induced migration, tube formation and proliferation of primary cultured human umbilical vascular endothelial cells (HUVECs) dose-dependently. Furthermore, Rd abrogated VEGF-induced sprouting of the vessels from aortic rings, and inhibited vascular formation in the Matrigel plug assay in vivo. Under normoxic or hypoxic conditions, Rd suppressed VEGF-induced activation of Akt/mammalian target of rapamycin (mTOR) signaling transduction cascades in HUVECs. When intraperitoneally administered to mice bearing human breast cancer (MDA-MB-231) cell xenografts, Rd significantly decreased the volume and the weight of solid tumors in a dose-dependent manner, and decreased tumor angiogenesis as less Ki67- and CD31-positive cells were found. Additionally, we found that Rd inhibited proliferation and induced apoptosis as well as the inhibition of Akt/mTOR/P70S6 kinase signaling in breast cancer cells. Collectively, our findings revealed that Rd may be a promising anti-angiogenic drug with significant antitumor activity in human breast cancer.