Open AccessVasoactive intestinal peptide increases apoptosis of hepatocellular carcinoma by inhibiting the cAMP /Bcl‐ xL pathway
Author(s) -
Hara Masaki,
Takeba Yuko,
Iiri Taroh,
Ohta Yuki,
Ootaki Masanori,
Watanabe Minoru,
Watanabe Daiki,
Koizumi Satoshi,
Otsubo Takehito,
Matsumoto Naoki
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13861
Subject(s) - vasoactive intestinal peptide , apoptosis , creb , receptor , antagonist , endocrinology , medicine , signal transduction , phosphorylation , cancer research , biology , chemistry , microbiology and biotechnology , neuropeptide , biochemistry , transcription factor , gene
Vasoactive intestinal peptide ( VIP ) is a modulator of inflammatory responses. VIP receptors are expressed in several tumor types, such as colorectal carcinoma. The study described herein was conducted to confirm the presence of VIP and its receptors ( VPAC 1 and VPAC 2) in surgically resected hepatocellular carcinoma ( HCC ) tissues and in the HCC cell line Huh7. The mechanism responsible for apoptosis of HCC cells was then examined because VIP treatment (10 −10 M) significantly suppressed proliferation of Huh7 cells. In examining apoptosis‐related proteins, we found caspase‐3 to be significantly increased and Bcl‐ xL and cyclic AMP ( cAMP ) response element‐binding protein ( CREB ) to be significantly decreased in Huh7 cells cultured with VIP . Furthermore, the CREB level and phosphorylation were reduced. These effects were reversed by the addition of VIP receptor antagonist or cAMP antagonist Rp‐ cAMPS . Pretreatment with cAMP analogue blocked the increased apoptosis, suggesting that VIP induces apoptosis via a PKA ‐independent signaling mechanism. Our data indicate that VIP prevents the progression of HCC by apoptosis through the cAMP /Bcl‐ xL pathway.