A tropomyosin-like Meretrix meretrix Linnaeus polypeptide inhibits the proliferation and metastasis of glioma cells via microtubule polymerization and FAK/Akt/MMPs signaling
A tropomyosin-like Meretrix meretrix Linnaeus polypeptide inhibits the proliferation and metastasis of glioma cells via microtubule polymerization and FAK/Akt/MMPs signaling
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原肌球蛋白样文蛤多肽通过微管聚合和 FAK/Akt/MMPs 信号传导抑制神经胶质瘤细胞的增殖和转移
DOI：
10.1016/j.ijbiomac.2019.12.158
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发表时间：
2020-02-15
影响因子：
8.2
通讯作者：
Wu, Ning
中科院分区：
文献类型：
--
作者：
Fan, Zhongjun;Xu, Qi;Wu, Ning
胶质母细胞瘤（GBM）是最常见、最具侵袭性和最致命的原发性肿瘤，由于现有的治疗方法无法控制其异常增殖和高侵袭性，预后不良。因此，针对这两个特征的治疗剂将更有效。本研究从文蛤（Meretrix meretrix Linnaeus）中分离纯化了一种具有抗肿瘤活性的多肽（MM 15），并对其进行了重组表达和鉴定。重组多肽（re-MM 15）可诱导U87细胞周期阻滞于G2/M期，并通过诱导微管蛋白聚合诱导细胞凋亡。另外。re-MM 15通过下调FAK/Akt/MMPs信号通路抑制U87细胞的迁移和侵袭。此外，体内分析表明，re-MM 15在U87异种移植模型中显著阻断肿瘤生长。总的来说，我们的研究结果表明，re-MM 15，在体外和体内抗GBM的特性，有希望作为一个新的抗癌候选GBM的潜力。(C)2019爱思唯尔B. V.保留所有权利。
Glioblastoma (GBM) represents the most common, aggressive and deadliest primary tumors with poor prognosis as available therapeutic approaches fail to control its aberrant proliferation and high invasiveness. Thus, the therapeutic agents targeting these two characteristics will be more effective. In present study, a novel polypeptide (MM15), which was originally purified from Meretrix meretrix Linnaeus and has been proven to possess potent antitumor activity by our laboratory, was recombinant expressed and identified as a tropomyosin homologous protein. The recombinant polypeptide (re-MM15) could induce the U87 cell cycle arrest in G2/M phase and cell apoptosis by inducing tubulin polymerization. Additionally. re-MM15 displayed the significant inhibition to the migration and invasion of U87 cells through downregulating FAK/Akt/MMPs signaling. Furthermore, the in vivo analysis suggested that re-MM15 significantly blocked tumor growth in U87 xenograft model. Collectively, our results indicated that re-MM15, with anti-GBM properties in vitro and in vivo, has promising potential as a new anticancer candidate for GBM. (C) 2019 Elsevier B.V. All rights reserved.