Open AccessNovel anti‐tumor mechanism of galanin receptor type 2 in head and neck squamous cell carcinoma cells
Author(s) -
Uehara Takayuki,
Kanazawa Takeharu,
Mizukami Hiroaki,
Uchibori Ryosuke,
Tsukahara Tomonori,
Urabe Masashi,
Kume Akihiro,
Misawa Kiyoshi,
Carey Thomas E.,
Suzuki Mikio,
Ichimura Keiichi,
Ozawa Keiya
Publication year - 2014
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.12315
Subject(s) - galanin , galanin receptor , head and neck squamous cell carcinoma , apoptosis , cancer research , biology , cell culture , cell growth , downregulation and upregulation , receptor , endocrinology , microbiology and biotechnology , medicine , neuropeptide , cancer , gene , head and neck cancer , biochemistry , genetics
Galanin and its receptors, GALR 1 and GALR 2, are known tumor suppressors and potential therapeutic targets in head and neck squamous cell carcinoma ( HNSCC ). Previously, we demonstrated that, in GALR 1‐expressing HNSCC cells, the addition of galanin suppressed tumor proliferation via upregulation of ERK 1/2 and cyclin‐dependent kinase inhibitors, whereas, in GALR 2‐expressing cells, the addition of galanin not only suppressed proliferation, but also induced apoptosis. In this study, we first transduced HEp ‐2 and KB cell lines using a recombinant adeno‐associated virus ( rAAV )‐green fluorescent protein ( GFP ) vector and confirmed a high GFP expression rate (>90%) in both cell lines at the standard vector dose. Next, we demonstrated that GALR 2 expression in the presence of galanin suppressed cell viability to 40–60% after 72 h in both cell lines. Additionally, the annexin V‐positive rate and sub‐G0/G1 phase population were significantly elevated in HEp ‐2 cells (mock vs GALR 2: 12.3 vs 25.0% ( P < 0.01) and 9.1 vs 32.0% ( P < 0.05), respectively) after 48 h. These changes were also observed in KB cells, although to a lesser extent. Furthermore, in HEp ‐2 cells, GALR 2‐mediated apoptosis was caspase‐independent, involving downregulation of ERK 1/2, followed by induction of the pro‐apoptotic Bcl‐2 protein, Bim. These results illustrate that transient GALR 2 expression in the presence of galanin induces apoptosis via diverse pathways and serves as a platform for suicide gene therapy against HNSCC .