Open AccessHMQ ‐T‐B10 induces human liver cell apoptosis by competitively targeting EphrinB2 and regulating its pathway
Author(s) -
Dai Bingling,
Shi Xianpeng,
Ma Nan,
Ma Weina,
Zhang Yanmin,
Yang Tianfeng,
Zhang Jie,
He Langchong
Publication year - 2018
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.13729
Subject(s) - apoptosis , gene knockdown , cancer research , liver cancer , cancer cell , cancer , cell growth , hepatocellular carcinoma , biology , cell , in vivo , signal transduction , microbiology and biotechnology , chemistry , biochemistry , genetics
Hepatocellular carcinoma ( HCC ) is a highly prevalent cancer worldwide and it is necessary to discover and develop novel preventive strategies and therapeutic approaches for HCC . Herein, we report that EphrinB2 expression is correlated with liver cancer progression. Moreover, by using phosphorylated proteomics array, we reveal a pro‐apoptosis protein whose phosphorylation and activation levels are up‐regulated upon EphrinB2 knockdown. These results suggest that EphrinB2 may act as an anti‐apoptotic protein in liver cancer cells. We also explored the therapeutic potential of HMQ ‐T‐B10 (B10), which was designed and synthesized in our laboratory, for HCC and its underlying mechanisms in vitro and in vivo. Our data demonstrate that B10 could bind EphrinB2 and show inhibitory activity on human liver cancer cells. Moreover, induction of human liver cancer cell apoptosis by B10 could be augmented upon EphrinB2 knockdown. B10 inhibited HCC cell growth and induced HCC cell apoptosis by repressing the EphrinB2 and VEGFR 2 signalling pathway. Growth of xenograft tumours derived from Hep3B in nude mice was also significantly inhibited by B10. Collectively, these findings highlight the potential molecular mechanisms of B10 and its potential as an effective antitumour agent for HCC .