Novel anti-tumor mechanism of galanin receptor type 2 in head and neck squamous cell carcinoma cells.
Novel anti-tumor mechanism of galanin receptor type 2 in head and neck squamous cell carcinoma cells.
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DOI：
10.1111/cas.12315
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发表时间：
2014-01
期刊：
影响因子：
5.7
通讯作者：
Ozawa K
中科院分区：
文献类型：
--
作者：
Uehara T;Kanazawa T;Mizukami H;Uchibori R;Tsukahara T;Urabe M;Kume A;Misawa K;Carey TE;Suzuki M;Ichimura K;Ozawa K
甘丙肽及其受体GALR1和GALR2是已知的肿瘤抑制因子和头颈部鳞状细胞癌(HNSCC)的潜在治疗靶点。在此之前，我们已经证明，在表达GALR1的HNSCC细胞中，甘丙素的加入通过上调ERK1/2和细胞周期蛋白依赖的激酶抑制剂来抑制肿瘤的增殖，而在表达GALR2的细胞中，甘丙素的加入不仅抑制了细胞的增殖，而且还诱导了细胞的凋亡。在这项研究中，我们首先使用重组腺相关病毒(RAAV)-绿色荧光蛋白(GFP)载体转导Hep-2和KB细胞，并证实在标准载体剂量下这两种细胞都有高GFP表达(>；90%)。接下来，我们证明了在甘丙肽存在的情况下，GALR2的表达在72小时后将两种细胞系的细胞存活率抑制到40-60%。48h后，Hep-2细胞膜联蛋白V阳性细胞率和亚G0/G1期细胞数显著增加(MOCK vs GALR2：12.3vs25.0%(P<；0.01)和9.1vs32.0%(P<；0.05)。KB细胞也观察到这些变化，但变化较小。此外，在Hep-2细胞中，GALR2介导的凋亡不依赖于caspase，包括下调ERK1/2，然后诱导促凋亡的Bcl-2蛋白Bim。这些结果表明，在甘丙肽存在的情况下，GALR2的瞬时表达通过多种途径诱导细胞凋亡，为自杀基因治疗HNSCC提供了一个平台。
Galanin and its receptors, GALR1 and GALR2, are known tumor suppressors and potential therapeutic targets in head and neck squamous cell carcinoma (HNSCC). Previously, we demonstrated that, in GALR1-expressing HNSCC cells, the addition of galanin suppressed tumor proliferation via upregulation of ERK1/2 and cyclin-dependent kinase inhibitors, whereas, in GALR2-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 GALR2 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 GALR2: 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, GALR2-mediated apoptosis was caspase-independent, involving downregulation of ERK1/2, followed by induction of the pro-apoptotic Bcl-2 protein, Bim. These results illustrate that transient GALR2 expression in the presence of galanin induces apoptosis via diverse pathways and serves as a platform for suicide gene therapy against HNSCC.
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DOI：
10.1186/1758-3284-2-8
发表时间：
2010-04-14
期刊：
Head & neck oncology
影响因子：
--
作者：
Goerner M;Seiwert TY;Sudhoff H
通讯作者：
Sudhoff H
影响因子：
7.3
作者：
Hill, SJ
通讯作者：
Hill, SJ
影响因子：
4
作者：
Fushimi, Kazunari;Nakashima, Shigeru;Shimizu, Katsuji
通讯作者：
Shimizu, Katsuji
影响因子：
12.4
作者：
Muramatsu, Shin-ichi;Fujimoto, Ken-ichi;Nakano, Imaharu
通讯作者：
Nakano, Imaharu
影响因子：
4.8
作者：
Barbieri, Federica;Pattarozzi, Alessandra;Florio, Tullio
通讯作者：
Florio, Tullio