Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
Biological Faculty, Moscow State University, Moscow, Russia.
Dokl Biochem Biophys. 2020 Jul;493(1):211-214. doi: 10.1134/S1607672920040134. Epub 2020 Sep 7.
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.
α7 型烟碱型乙酰胆碱受体 (α7-nAChR) 被认为是癌症治疗有前途的药理学靶点。我们之前已经表明，人蛋白 SLURP-1 的重组类似物 (rSLURP-1) 通过与 α7-nAChR 相互作用并下调该受体的表达，有效地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，该受体在神经胶质瘤发展中的作用尚不清楚。首次表明 rSLURP-1 可显著抑制神经胶质瘤模型细胞 U251 MG 和 A172 的生长，最大抑制率可达约 70%，与选择性 α7-nAChR 抑制剂 α-银环蛇毒素的作用相当。rSLURP-1 对 U251 MG 和 A172 细胞的半最大有效浓度分别为 2.82 ± 0.2 和 8.9 ± 0.3 nM。rSLURP-1 与 nAChR 抑制剂美加明共同孵育可减弱 rSLURP-1 的抗增殖活性，表明 nAChR 是 rSLURP-1 在神经胶质瘤中作用的分子靶标。
