淫羊藿素抑制细胞周期蛋白依赖性激酶2（CDK2）的表达和活性以干扰肿瘤进展。
Icaritin inhibits CDK2 expression and activity to interfere with tumor progression.
作者信息
Zhang Chao, Wang Xin, Zhang Chuanbao
机构信息
National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, P. R. China.
Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing Key Laboratory of Diabetes Research and Care, Beijing, China.
出版信息
iScience. 2022 Aug 22;25(9):104991. doi: 10.1016/j.isci.2022.104991. eCollection 2022 Sep 16.
Icaritin has shown antitumor activity in a variety of human solid tumors and myeloid leukemia cells. However, the direct target of icaritin and the underlying mechanisms remain unclear. In our study, CDK2 was found to be a direct target of icaritin in tumor cells. On one hand, icaritin interacted with CDK2 and interfered with CDK2/CyclinE complex formation, resulting in downregulation of CDK2 activity as illustrated with attenuated phosphorylation of FOXO1, Rb, and P27, and E2F/Rb dissociation. On the other hand, icaritin reduced the stability and translation efficiency of CDK2-mRNA by modulating microRNA-597 expression. To be of functional importance, icaritin inhibited proliferation and promoted apoptosis of tumor cells and , which was consistent with CDK2 inhibitors-k03861. Our data revealed CDK2 as the direct target of icaritin for its antitumor effects, which may suggest new therapeutics of icaritin or combinational therapeutics involving both icaritin and CDK2 inhibitors for cancers.
淫羊藿素在多种人类实体瘤和髓系白血病细胞中显示出抗肿瘤活性。然而，淫羊藿素的直接靶点及潜在机制仍不清楚。在我们的研究中，发现细胞周期蛋白依赖性激酶2（CDK2）是淫羊藿素在肿瘤细胞中的直接靶点。一方面，淫羊藿素与CDK2相互作用，干扰CDK2/细胞周期蛋白E复合物的形成，导致CDK2活性下调，表现为叉头框蛋白O1（FOXO1）、视网膜母细胞瘤蛋白（Rb）和P27的磷酸化减弱，以及E2F/Rb解离。另一方面，淫羊藿素通过调节微小RNA-597的表达降低CDK2-mRNA的稳定性和翻译效率。为了验证其功能重要性，淫羊藿素抑制肿瘤细胞增殖并促进其凋亡，这与CDK2抑制剂k03861的作用一致。我们的数据揭示了CDK2是淫羊藿素发挥抗肿瘤作用的直接靶点，这可能为淫羊藿素或涉及淫羊藿素与CDK2抑制剂联合使用的癌症联合治疗提供新的治疗方法。
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