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东亚钳蝎毒素CT和¹²⁵I-东亚钳蝎毒素CT通过基质金属蛋白酶-2在体外抑制胶质瘤细胞的侵袭。

BmK CT and 125I-BmK CT suppress the invasion of glioma cells in vitro via matrix metalloproteinase-2.

作者信息

Sun Na, Zhao Lingzhou, Qiao Wenli, Xing Yan, Zhao Jinhua

机构信息

Department of Nuclear Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.

出版信息

Mol Med Rep. 2017 May;15(5):2703-2708. doi: 10.3892/mmr.2017.6284. Epub 2017 Mar 3.

Abstract

Chlorotoxin (CTX) is an established blocker of small‑conductance Cl‑ channels and has previously been demonstrated to inhibit the invasion of glioma cells. Buthus martensii Karsch chlorotoxin‑like toxin (BmK CT) is the first chlorotoxin-like peptide. The present study aimed to determine the inhibitory effect of BmK CT on the invasive ability of glioma cells, using a Transwell assay. BmK CT was subsequently radiolabeled with radionuclide 125I and its activity was compared with BmK CT. Additionally, the underlying anti‑invasive mechanism of BmK CT and 125I‑BmK CT on glioma cells was investigated by ELISA and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). It was revealed that BmK CT and 125I‑BmK CT were able to inhibit the invasion of glioma cells and that 125I‑BmK CT was superior to BmK CT. Consistent with the results of the Transwell assay, matrix metalloproteinase‑2 (MMP‑2) secretion by glioma cells was significantly reduced following treatment with BmK CT or 125I‑BmK CT (P<0.05). However, no significant differences in MMP-2 mRNA expression levels were identified by RT‑qPCR (P>0.05). In conclusion, the present study demonstrated that BmK CT and 125I‑BmK CT reduced the invasion of glioma cells via downregulation of MMP-2 expression. However, inhibition of the invasion of glioma cells was not demonstrated at the mRNA level.

摘要

氯毒素(CTX)是一种已被证实的小电导氯离子通道阻滞剂,先前已被证明可抑制胶质瘤细胞的侵袭。东亚钳蝎氯毒素样毒素(BmK CT)是首个氯毒素样肽。本研究旨在采用Transwell实验测定BmK CT对胶质瘤细胞侵袭能力的抑制作用。随后,用放射性核素125I对BmK CT进行放射性标记,并将其活性与BmK CT进行比较。此外,通过酶联免疫吸附测定(ELISA)和逆转录-定量聚合酶链反应(RT-qPCR)研究了BmK CT和125I-BmK CT对胶质瘤细胞的潜在抗侵袭机制。结果显示,BmK CT和125I-BmK CT均能抑制胶质瘤细胞的侵袭,且125I-BmK CT优于BmK CT。与Transwell实验结果一致,用BmK CT或125I-BmK CT处理后,胶质瘤细胞基质金属蛋白酶-2(MMP-2)的分泌显著减少(P<0.05)。然而,RT-qPCR未发现MMP-2 mRNA表达水平有显著差异(P>0.05)。总之,本研究表明,BmK CT和125I-BmK CT通过下调MMP-2表达降低了胶质瘤细胞的侵袭。然而,在mRNA水平未证实对胶质瘤细胞侵袭的抑制作用。

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