Anti-angiogenesis effect of trichosanthin and the underlying mechanism

作者：He Dongxu; Jin Jian; Zheng Yongtang; Bruce Iain C; Tam Siucheung^*; Ma Xin

来源：Biochemical and Biophysical Research Communications, 2013, 430(2): 735-740.

DOI：10.1016/j.bbrc.2012.11.080

• Tumor angiogenesis
• Trichosanthin
• Vascular endothelial growth factor
• Extracellular signal-regulated kinases

The growth and metastasis of tumors depend on angiogenesis. Tumor angiogenesis is initiated by the secretion of growth factors from tumor cells; downstream signals are then triggered in pre-existing blood vessels to sprout a new vascular network. Trichosanthin (TCS) is a type I ribosome-inactivating protein that has anti-tumor activity, but the underlying mechanism remains unclear. In this study, we found that a non-toxic dose of TCS decreased the wound-healing and the migration of H5V mouse heart capillary endothelial cells (ECs) induced by human choriocarcinoma (JAR) cells, as well as the JAR-induced angiogenesis of rat third-order mesenteric arteries. TCS was effective on both tumor cells and ECs/arteries. First, TCS decreased vascular endothelial growth factor transcription and secretion by JAR cells. Second, TCS consequently inhibited the tumor cell-induced, extracellular signal-regulated kinase-mediated angiogenic signal in ECs and blood vessels. In conclusion, the ability of TCS to inhibit tumor angiogenesis contributes to its anti-tumor activity.

• 出版日期2013-1-11
• 单位浙江大学; 中国科学院; 中国科学院昆明动物研究所; 江南大学; 香港中文大学