Fisetin Modulates Human Oral Squamous Cell Carcinoma Proliferation by Blocking PAK4 Signaling Pathways
Fisetin Modulates Human Oral Squamous Cell Carcinoma Proliferation by Blocking PAK4 Signaling Pathways
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Fisetin 通过阻断 PAK4 信号通路调节人口腔鳞状细胞癌增殖
DOI：
10.2147/dddt.s229270
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发表时间：
2020-01-01
影响因子：
4.8
通讯作者：
Dai, Wei
中科院分区：
文献类型：
--
作者：
Li, Yanshu;Jia, Shiheng;Dai, Wei
目的口腔鳞状细胞癌(OSCC)是世界范围内致死和致病的主要原因。迫切需要寻找能够抑制口腔鳞癌发生的生物活性分子和潜在的靶基因。Fisetin(3，7，3‘，4’-四羟基黄酮)是一种天然存在的黄酮类化合物，已被证明在口腔鳞癌中具有抗增殖活性，但其分子机制尚不清楚。方法采用集落形成实验、细胞活力实验、Boyden小室实验、伤口愈合实验和裸鼠移植瘤实验，检测Fesetin对口腔鳞癌细胞的体内外影响。Western印迹分析检测相应蛋白的表达。结果鱼腥草素通过抑制PAK4的表达，抑制细胞增殖，促进细胞凋亡。此外，非瑟素处理通过阻断PAK4信号通路来减弱细胞迁移。此外，裸鼠移植瘤在体内也显示出非瑟素的抗肿瘤生长作用。结论非瑟素可能通过靶向PAK4信号通路，为口腔鳞癌的治疗提供了一种潜在的策略。
Objective Human oral squamous cell carcinoma (OSCC) is a major cause of mortality and morbidity worldwide. There is an urgent need to identify bioactive molecules and potential target genes that could inhibit carcinogenesis for OSCC therapy. Fisetin (3,7,3′,4′-tetrahydroxyflavone), a naturally occurring flavonoid, has been previously shown to have anti-proliferative activities in OSCC; however, its molecular mechanism is unknown. Methods Colony formation, cell viability, Boyden chamber, wound healing, and tumor xenograft assays were used to detect the impact of fisetin on OSCC cells in vitro and in vivo. Western blot analysis was used to examine the corresponding protein expression. Results Fisetin treatment significantly inhibited proliferation and promoted apoptosis by repressing PAK4 expression. Moreover, fisetin treatment attenuated cell migration by blocking PAK4 signaling pathways. In addition, the tumor xenograft showed anti-tumor growth effects of fisetin exposure in vivo. Conclusion Fisetin may represent a potential therapeutic strategy for human OSCC by targeting PAK4 signaling pathways.