Fisetin Inhibits Trypsin Activity and Suppresses the Growth of Colorectal Cancer in Vitro and in Vivo
Fisetin Inhibits Trypsin Activity and Suppresses the Growth of Colorectal Cancer in Vitro and in Vivo
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DOI：
10.1177/1934578x221115511
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发表时间：
2022-08
影响因子：
1.8
通讯作者：
Lin Li;Min Wang;Hongyan Yang;Yuting Li;Xiaoling Huang;Jialiang Guo;Zheng Liu
中科院分区：
文献类型：
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作者：
Lin Li;Min Wang;Hongyan Yang;Yuting Li;Xiaoling Huang;Jialiang Guo;Zheng Liu
结直肠癌是一种发病率高、预后差的恶性肿瘤。迫切需要更安全和有效的治疗方法。胰蛋白酶在肿瘤的增殖和转移过程中起重要作用，因此，通过调节其活性来控制肿瘤是可能的。非瑟酮是一种具有胰蛋白酶抑制作用的黄酮类化合物，是从45种中药中筛选出来的。然而，非瑟酮对结直肠癌的作用和机制尚未得到很好的研究。在这项研究中，我们评估了非瑟酮对2种不同的结直肠癌细胞系的影响。非瑟酮能明显抑制大肠癌细胞的增殖和迁移，并诱导细胞凋亡和G0/G1期阻滞，且呈剂量依赖性。机制研究表明，这些作用部分通过涉及细胞周期调节因子p21、p27、cyclinD1和NF-κ B（NF-κ B）p65的信号通路介导。非瑟酮给药还显著抑制了接种人HCT 116细胞的荷瘤NOD/Shi-scid-IL2R γ（null）（NOG）小鼠的肿瘤生长。在给定剂量下，非瑟酮在大鼠中未引起显著的急性或慢性毒性。这些数据为CRC提供了潜在的治疗策略。
Colorectal cancer (CRC) is a malignant tumor with high incidence and bad prognosis. Therapies, which are more safe and effective, are urgently needed. Trypsin is proved to be crucial to cancer proliferation and migration, therefore, it is possible to control cancers by modulating its activity. Fisetin is a flavone with trypsin inhibition properties that was screened from more than 45 compounds derived from traditional Chinese medicine (TCM). However, the effects and mechanisms of fisetin on CRC have not been well investigated. In this study, we evaluated the effects of fisetin on 2 different CRC cell lines. Fisetin remarkably inhibited CRC cell proliferation and migration, as well as induced cell apoptosis and Go/G1 phase arrest in a dose-dependent manner. Mechanistic studies revealed that these effects were mediated partially through signaling pathways involving cell cycle regulators p21, p27, cyclinD1, and NF kappa B (NF-κB) p65. Administration of fisetin also significantly suppressed the tumor growth in tumor-bearing NOD/Shi-scid-IL2R gamma (null) (NOG) mice that had been inoculated with human HCT116 cells. Fisetin at the given dosage did not induce significant acute or chronic toxicity in rats. These data provide a potential therapeutic strategy for CRC.