Abstract

The alpha7 nicotinic acetylcholine receptor (α7-nAChR) is considered a promising pharmacological target for the carcinoma therapy. We have previously shown that the recombinant analogue of the human protein SLURP-1 (rSLURP-1) effectively inhibits the growth of carcinomas of various origins via the interaction with α7-nAChR and down-regulation of expression of this receptor. Expression of α7-nAChR is increased in gliomas compared to healthy human brain tissues; however, the role of this receptor in the gliomas development is poorly understood. It was shown for the first time that rSLURP-1 significantly inhibits the growth of glioma model cells U251 MG and A172 up to ∼70%, which is comparable with the effect of α-bungarotoxin, a selective α7-nAChR inhibitor. The half-maximum effective concentrations of rSLURP-1 for U251 MG and A172 cells were 2.82 ± 0.2 and 8.9 ± 0.3 nM, respectively. Coincubation of U251 MG cells with rSLURP-1 and the nAChR inhibitor mecamylamine attenuates the antiproliferative activity of rSLURP-1, indicating nAChR as a molecular target for the rSLURP-1 action in gliomas.

中文翻译：

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人蛋白SLURP-1的重组类似物抑制U251 MG和A172胶质瘤细胞的生长。

摘要

α7烟碱乙酰胆碱受体（α7-nAChR）被认为是癌症治疗的有希望的药理靶标。先前我们已经表明，人类蛋白SLURP-1的重组类似物（rSLURP-1）通过与α7-nAChR的相互作用以及该受体表达的下调，有效抑制了各种来源的癌的生长。与健康的人脑组织相比，神经胶质瘤中α7-nAChR的表达增加；然而，对该受体在神经胶质瘤发展中的作用了解甚少。首次显示，rSLURP-1显着抑制神经胶质瘤模型细胞U251 MG和A172的生长，直至约70％，这与选择性α7-nAChR抑制剂α-真菌毒素的作用相当。对于U251 MG和A172细胞，rSLURP-1的半最大有效浓度为2。分别为82±0.2和8.9±0.3 nM。U251 MG细胞与rSLURP-1和nAChR抑制剂美卡明胺的共孵育减弱了rSLURP-1的抗增殖活性，表明nAChR作为神经胶质瘤中rSLURP-1作用的分子靶标。