Open AccessInhibition of HBV-induced angiogenesis by ibuprofen: Role of HBx
Author(s) -
Jianhua Zhang,
William Wei Ning Chen
Publication year - 2012
Publication title -
interventional medicine and applied science/interventional medicine and applied science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.195
H-Index - 14
eISSN - 2061-5094
pISSN - 2061-1617
DOI - 10.1556/imas.4.2012.1.5
Subject(s) - hbx , angiogenesis , hepatitis b virus , hepatocellular carcinoma , ibuprofen , cancer research , nf κb , medicine , microbiology and biotechnology , inflammation , virology , virus , biology , pharmacology , immunology
Chronic hepatitis B virus (HBV) carriers may develop hepatocellular carcinoma (HCC) by a wide range of mechanisms including angiogenesis. We show that HBV replication induces the expression of angiogenic proteins interleukin 6 (IL6) and cyclooxygenase-2 (Cox2). Interestingly, ibuprofen (a Cox2 inhibitor) is found to attenuate the levels of IL6 and Cox 2 which are induced by HBV replication. The mechanism of attenuation of angiogenic proteins by ibuprofen was further investigated. Our results show that HBx is involved in the increase of the expression of Cox2 through the NFκB pathway. However, the expression of Cox2 is decreased when the HBx-expressing cells are incubated with ibuprofen. The contrasting effect of HBx on Cox2 is found to be determined by differential dimer formation among the members of the NFκB family of proteins, including NFκB, RelA, and C-rel. Specifically, HBx alone results in dimer formation between NFκB and RelA, while the combined presence of HBx and ibuprofen leads to the formation of NFκB and C-rel. Additional information on the interaction network involving HBx, ibuprofen, and NFκB pathways is revealed by two-dimensional liquid chromatography-tandem mass spectrometry proteomics analysis. Taken together, our findings provide new insights on the angiogenesis induced by HBV replication.