title: Brucine suppresses colon cancer cells growth via mediating KDR signalling pathway.
abstract: Angiogenesis plays an important role in colon cancer development. This study aimed to demonstrate the effect of brucine on tumour angiogenesis and its mechanism of action. The anti-angiogenic effect was evaluated on the chicken chorioallantoic membrane (CAM) model and tube formation. The mechanism was demonstrated through detecting mRNA and protein expressions of VEGFR2 (KDR), PKCα, PLCγ and Raf1 by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot (WB), as well as expressions of VEGF and PKCβ and mTOR by ELISA and WB. The results showed that brucine significantly reduced angiogenesis of CAM and tube formation, inhibited the VEGF secretion and mTOR expression in LoVo cell and down-regulated the mRNA and phosphorylation protein expressions of KDR, PKCα, PLCγ and Raf1. In addition, the effects of brucine on KDR kinase activity, viability of LoVo cell and gene knockdown cell were detected with the Lance™ assay, WST-1 assay and instantaneous siRNA. Compared to that of normal LoVo cells, the inhibition on proliferation of knockdown cells by brucine decreased significantly. These results suggest that brucine could inhibit angiogenesis and be a useful therapeutic candidate for colon cancer intervention.
authors.affiliation: School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Luo
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.forename: Yingzhuan
authors.initials: Y
authors.lastname: Zhan
authors.forename: Dongdong
authors.initials: D
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D017931:DNA Primers; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D013331:Strychnine / Q000031:analogs & derivatives* / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D017931:DNA Primers; D034741:RNA, Small Interfering; C083806:brucine; D040301:Vascular Endothelial Growth Factor Receptor-2; D013331:Strychnine
keywords: Angiogenesis; Brucine; KDR; LoVo cells; Phosphorylation
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