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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

Disintegrin Tablysin-15通过阻断FAK / Akt / ERK和NF-κB信号传导抑制黑色素瘤细胞的癌症特征

卷 20, 期 4, 2020

页: [306 - 315] 页: 10

弟呕挨: 10.2174/1568009620666200101094736

价格: $65

摘要

背景：整联蛋白是关键的抗癌治疗靶标。我们先前显示，在新的结构环境中，tablysin-15是具有Arg-Gly-Asp主题的整联蛋白拮抗剂。目的：在这里我们研究了新霉素15在黑色素瘤细胞中的抗癌作用及其作用机制。 方法：采用细胞粘附，竞争结合，细胞生存力和ATP化学发光分析法分析细胞溶素15与αVβ3整联蛋白的结合及其表型效应。进行伤口愈合，穿透孔和酶谱分析以检测运动性和基质金属蛋白酶-2 / -9活性。 PARP和caspase-3裂解用于细胞凋亡测定，而LDH释放和流式细胞仪用于坏死和细胞周期分析。分别通过qRT-PCR和蛋白质印迹法检测靶分子的mRNA和蛋白质的表达。 结果：Tablysin-15剂量依赖性地通过整合素αvβ3抑制M21细胞的增殖，迁移和侵袭。 tablysin-15引起的增殖抑制作用归因于G0 / G1期停滞，而不是细胞凋亡或坏死。此外，tablysin-15抑制MMP-2 /-9活性以及MMP-2 / -9和COX-2的mRNA表达，但在M21细胞中上调TIMP-1。同时，tablysin-15抑制了细胞周期蛋白D1 / E和CDK 2/6的表达，FAK，Akt和ERK的磷酸化以及NF-κB的核易位，同时增加了CDK抑制剂p21waf1 / C1的表达。综上所述，tablysin-15可能通过与αVβ3整联蛋白竞争而抑制黑素瘤细胞的转移和增殖，从而阻断FAK相关的信号通路和NF-κB的核易位。 结论：Tablysin-15对M21黑色素瘤细胞具有可靠的抗癌作用，表明tablysin-15是一种有前途的抗肿瘤药物。

关键词: Tablysin-15，αvβ3，黑色素瘤，RGD，FAK / Akt / ERK，NF-κB。

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