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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

EH-42：一种新型小分子通过抑制STAT3信号通路诱导细胞凋亡并抑制人肝癌细胞的迁移和侵袭

卷 19, 期 7, 2019

页: [583 - 593] 页: 11

弟呕挨: 10.2174/1568009619666181226094814

价格: $65

摘要

背景：由于信号转导和转录激活因子3（STAT3）在肝细胞癌（HCC）中异常激活，并在该肿瘤进展中起关键作用。 已经认为抑制STAT3信号传导途径是抑制HCC发展的有效治疗策略。 目的：在本研究中，我们研究了EH-42对HCC细胞的抗癌作用，并试图解释其潜在机制。 方法：采用MTT法，结肠形成法和AnnexinV-FITC / PI双染法检测EH-42对细胞生长和存活的影响。 进行伤口愈合测定和transwell侵袭测定以评估EH-42对细胞迁移和侵袭的影响。 进行蛋白质印迹分析以分析EH-42对相对蛋白质的影响。 结果：根据MTT法，结肠形成实验和AnnexinV-FITC / PI双染试验，EH-42能够以剂量依赖的方式抑制HCC细胞的生长并诱导其凋亡。 进一步的免疫印迹实验表明，EH-42对细胞生长和存活的抑制作用是通过激活caspase 3/9，抑制磷酸化STAT3（Tyr 705）和下调抗凋亡蛋白如Bcl-2 / Bcl-xL引起的。 此外，在伤口愈合测定和transwell侵袭测定中，EH-42也抑制HCC细胞的迁移和侵袭能力。 潜在的机制是EH-42可通过逆转上皮 - 间质转化和下调MMPs的分泌来抑制HCC转移。 结论：总之，这些发现表明EH-42可能是HCC治疗的潜在治疗药物。

关键词: STAT3，细胞凋亡，迁移，侵袭，肝细胞癌。

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