Open AccessBrucine suppresses colon cancer cells growth via mediating KDR signalling pathway
Author(s) -
Luo Wenjuan,
Wang Xiaoli,
Zheng Lei,
Zhan Yingzhuan,
Zhang Dongdong,
Zhang Jie,
Zhang Yanmin
Publication year - 2013
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12108
Subject(s) - brucine , angiogenesis , chorioallantoic membrane , gene knockdown , pi3k/akt/mtor pathway , cell growth , cancer research , chemistry , microbiology and biotechnology , biology , signal transduction , cell culture , pharmacology , biochemistry , genetics , strychnine
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 VEGFR 2 ( KDR ), PKC α, PLC γ and Raf1 by reverse transcription‐polymerase chain reaction ( RT ‐ PCR ) and Western blot ( WB ), as well as expressions of VEGF and PKC β 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 , PKC α, PLC γ 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 si RNA . 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.