Oridonin inhibits VEGF‑A‑associated angiogenesis and epithelial‑mesenchymal transition of breast cancer in vitro and in vivo

作者: Chunyu Li , Qi Wang , Shen Shen , Xiaolu Wei , Guoxia Li

DOI: 10.3892/OL.2018.8943

关键词: MetastasisMolecular medicineAngiogenesisEpithelial–mesenchymal transitionOncogeneVEGF Signaling PathwayTube formationChemistryGrowth factorCancer research

摘要: Metastasis is the primary cause of mortality in patients with breast cancer and lacks effective therapeutic agents. Oridonin, an active diterpenoid compound isolated from Rabdosia rubescens, was identified to be most potent anti-tumor ingredient. However, molecular mechanisms responsible for its anti-metastatic effects remain unclear. In present study, oridonin significantly suppressed migration, invasion adhesion MDA-MB-231 4T1 cells, inhibited tube formation human umbilical vein endothelial cells a dose-dependent manner. The expression levels epithelial-mesenchymal transition (EMT)-associated marker hypoxia inducible factor 1α (HIF-1α)/vascular endothelium growth (VEGF) signaling pathway mRNA proteins were determined by reverse transcription-quantitative polymerase chain reaction western blotting, respectively vitro. results demonstrated that effectively EMT as significant increases E-cadherin, decreased N-cadherin, Vimentin Snail. addition, exerted anti-angiogenesis activity through decreasing HIF-1α, VEGF-A VEGF receptor-2 protein expression. Furthermore, decrease micro-vessel density evidenced cluster differentiation 31, neovasculature. brief, inhibits tumor cell adhesion, well angiogenesis, which are mediated suppressing HIF-1α/VEGF pathway. study suggest may promising agent treatment.

参考文章(31)
Jin-Mei Yu, Wei Sun, Fang Hua, Jing Xie, Heng Lin, Dan-Dan Zhou, Zhuo-Wei Hu, BCL6 induces EMT by promoting the ZEB1-mediated transcription repression of E-cadherin in breast cancer cells. Cancer Letters. ,vol. 365, pp. 190- 200 ,(2015) , 10.1016/J.CANLET.2015.05.029
TAO HUANG, ZHIJUN CHEN, LIPING FANG, Curcumin inhibits LPS-induced EMT through downregulation of NF-κB-Snail signaling in breast cancer cells. Oncology Reports. ,vol. 29, pp. 117- 124 ,(2013) , 10.3892/OR.2012.2080
Takayuki Ikezoe, Sophie Chen, Xian-Jun Tong, David Heber, Hirokuni Taguchi, H. Koeffler, Oridonin induces growth inhibition and apoptosis of a variety of human cancer cells International Journal of Oncology. ,vol. 23, pp. 1187- 1193 ,(2003) , 10.3892/IJO.23.4.1187
Zechun Kang, Wanglin Jiang, Haiyun Luan, Feng Zhao, Shuping Zhang, Cornin induces angiogenesis through PI3K-Akt-eNOS-VEGF signaling pathway. Food and Chemical Toxicology. ,vol. 58, pp. 340- 346 ,(2013) , 10.1016/J.FCT.2013.05.017
Flávia Cristine Mascia Lopes, Regiane Ferreira, Dulcinéia Martins Albuquerque, Angélica A. Antoniellis Silveira, Raquel Costa, Raquel Soares, Fernando Ferreira Costa, Nicola Conran, In vitro and in vivo anti-angiogenic effects of hydroxyurea Microvascular Research. ,vol. 94, pp. 106- 113 ,(2014) , 10.1016/J.MVR.2014.05.009
Yanmin Dong, Tao Zhang, Jingjie Li, Huayun Deng, Yajuan Song, Dong Zhai, Yi Peng, Xiaoling Lu, Mingyao Liu, Yongxiang Zhao, Zhengfang Yi, Oridonin inhibits tumor growth and metastasis through anti-angiogenesis by blocking the Notch signaling. PLOS ONE. ,vol. 9, ,(2014) , 10.1371/JOURNAL.PONE.0113830
Hua Liu, Changlin Qian, Zhiyong Shen, Anti-tumor activity of oridonin on SNU-5 subcutaneous xenograft model via regulation of c-Met pathway Tumor Biology. ,vol. 35, pp. 9139- 9146 ,(2014) , 10.1007/S13277-014-2178-4
Yupei Li, Deni S Galileo, Soluble L1CAM promotes breast cancer cell adhesion and migration in vitro, but not invasion. Cancer Cell International. ,vol. 10, pp. 34- 34 ,(2010) , 10.1186/1475-2867-10-34