M2 receptor activation inhibits cell cycle progression and survival in human glioblastoma cells.
M2 receptor activation inhibits cell cycle progression and survival in human glioblastoma cells.
复制标题
DOI：
10.1111/jcmm.12038
复制
发表时间：
2013-04
影响因子：
5.3
通讯作者：
Tata AM
中科院分区：
文献类型：
--
作者：
Ferretti M;Fabbiano C;Di Bari M;Conte C;Castigli E;Sciaccaluga M;Ponti D;Ruggieri P;Raco A;Ricordy R;Calogero A;Tata AM
毒蕈碱受体，在几个原发性和转移性肿瘤中表达，似乎与它们的生长和繁殖有关。在这项工作中，我们已经证明，M2毒蕈碱受体表达的胶质母细胞瘤的人类标本和胶质母细胞瘤细胞系。此外，我们已经表征了M2激动剂槟榔碱对两种不同的胶质母细胞瘤细胞系（U251 MG和U87 MG）和从不同的人类活检获得的原代培养物中细胞生长和存活的影响。细胞生长分析表明，M2激动剂槟榔碱强烈降低神经胶质瘤细胞系和原代培养物中的细胞增殖。这种效应具有剂量和时间依赖性。流式细胞仪分析证实U87细胞和U251细胞周期分别停滞在G1/S期和G2/M期。细胞活力分析也表明槟榔碱诱导严重的凋亡，特别是在U251细胞中。此外，化学敏感性测定显示槟榔碱和替莫唑胺对神经胶质瘤细胞系具有相似的作用，尽管槟榔碱的IC 50值显著低于替莫唑胺。总之，我们首次报道了M2受体激活在抑制胶质瘤细胞生长和存活中具有相关作用，这表明M2可能是一个新的有趣的治疗靶点，用于胶质母细胞瘤治疗的研究。
Muscarinic receptors, expressed in several primary and metastatic tumours, appear to be implicated in their growth and propagation. In this work we have demonstrated that M2 muscarinic receptors are expressed in glioblastoma human specimens and in glioblastoma cell lines. Moreover, we have characterized the effects of the M2 agonist arecaidine on cell growth and survival both in two different glioblastoma cell lines (U251MG and U87MG) and in primary cultures obtained from different human biopsies. Cell growth analysis has demonstrated that the M2 agonist arecaidine strongly decreased cell proliferation in both glioma cell lines and primary cultures. This effect was dose and time dependent. FACS analysis has confirmed cell cycle arrest at G1/S and at G2/M phase in U87 cells and U251 respectively. Cell viability analysis has also shown that arecaidine induced severe apoptosis, especially in U251 cells. Chemosensitivity assays have, moreover, shown arecaidine and temozolomide similar effects on glioma cell lines, although IC50 value for arecaidine was significantly lower than temozolomide. In conclusion, we report for the first time that M2 receptor activation has a relevant role in the inhibition of glioma cell growth and survival, suggesting that M2 may be a new interesting therapeutic target to investigate for glioblastoma therapy.
登录
查看更多内容
DOI：
10.1152/ajpcell.2000.279.6.c2043
发表时间：
2000-12-01
影响因子：
5.5
作者：
Castigli, E;Arcuri, C;Bocchini, V
通讯作者：
Bocchini, V
影响因子：
4.1
作者：
Boss, A;Oppitz, M;Drews, U
通讯作者：
Drews, U
影响因子：
5.6
作者：
Jiménez, E;Montiel, M
通讯作者：
Montiel, M
影响因子：
5
作者：
Guizzetti, M;Costa, P;Costa, LG
通讯作者：
Costa, LG
影响因子：
--
作者：
Ma, W;Li, BS;Pant, HC
通讯作者：
Pant, HC