Antiangiogenic effects of oxymatrine on pancreatic cancer by inhibition of the NF-κB-mediated VEGF signaling pathway

Abstract

Oxymatrine, the main alkaloid component in the traditional Chinese herbal medicine Sophora japonica (Sophora flavescens Ait), has been reported to have antitumor properties. However, the mechanisms of action in human pancreatic cancer are not well established to date. In the present study, we investigated the antiangiogenic effects of oxymatrine on human pancreatic cancer as well as the possible mechanisms involved. The results of the cell viability assay showed that treatment of PANC-1 pancreatic cancer cells with oxymatrine resulted in cell growth inhibition in a dose- and time-dependent manner. To investigate the possible mechanisms involved in these events, we performed western blotting and reverse transcription-polymerase chain reaction (RT-PCR) analysis. The results revealed that oxymatrine decreased the expression of angiogenesis-associated factors, including nuclear factor κB (NF-κB) and vascular endothelial growth factor (VEGF). Finally, the antiproliferative and antiangiogenic effects of oxymatrine on human pancreatic cancer were further confirmed in pancreatic cancer xenograft tumors in nude mice. In conclusion, our studies for the first time suggest that oxymatrine has potential antitumor effects on pancreatic cancer via suppression of angiogenesis, probably through regulation of the expression of the NF-κB-mediated VEGF signaling pathway.

A map describing the association between effective components of traditional Chinese medicine and signaling pathways in cancer cells in vitro and in vivo

“…In human osteosarcoma MNNG/HOS cell line, oxymatrine induces mitochondria dependent apoptosis by inhibiting the PI3K/Akt pathway (15). In an in intro and in vivo experiment, oxymatrine shows an antiangiogenic effect on pancreatic cancer through inhibition of the NF-κB-mediated VEGF signaling pathway (16).…”

RETRACTED: Effects of Oxymatrine on the Proliferation and Apoptosis of Human Hepatoma Carcinoma Cells

“…Extensive research over the past decades have revealed various important pharmacological activities of oxymatrine under in vitro and in vivo conditions, including anti-inflammation, immunoregulatory, antihepatitis virus infection, antihepatic fibrosis, antianaphylaxis, and other immune regulation. [11][12][13][14][15] Recently, oxymatrine has been extensively studied for their cancer chemopreventive potential against various cancers, for instance, human pancreatic cancer, 16 gastric cancer, 17 breast cancer, 18 lung cancer, 19 osteosarcoma, 20 and leukemia. 21 However, the precise mechanisms underlying the anticancer activity of oxymatrine are largely unknown.…”

Oxymatrine Improves Intestinal Epithelial Barrier Function Involving NF-κB-Mediated Signaling Pathway in CCl4-Induced Cirrhotic Rats

“…It has been reported that oxymatrine protected animals against ischemia and reperfusion-induced liver, heart, and intestinal injuries involving extracellular signal regulated kinase, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinases signaling pathways [19]–[21]. In addition, the inhibitory effect of oxymatrine on NF-κB signaling pathway has been reported in pancreatic cancer [22] and cerebral ischemia in animals [23]. However, the effect of oxymatrine on NF-κB signaling pathway and the association with intestinal epithelial barrier dysfunction is unclear.…”