Wang Xian, Lin Xiao, Liu Yuxin, Ma Chunbo, Liu Mengchu, Bai Jiayu, Ye Yihan, Zhao Chengguang, Yang Lehe, Huang Xiaoying, Wang Liangxing
Pulmonary Division, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325035, China; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Shanghai Fengxian District Central Hospital, No. 6600, Nanfeng Highway, Fengxian District, Shanghai 201499, China.
Pulmonary Division, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325035, China.
Transl Oncol. 2025 Jun;56:102382. doi: 10.1016/j.tranon.2025.102382. Epub 2025 Apr 11.
The aim of this study was to investigate the anti-tumor effects and mechanisms of Raddeanin A in NSCLC in vitro and in vivo.
The effects of Raddeanin A on cell cycle progression, proliferation, migration and invasion of NSCLC were assessed by flow cytometry and cell biological assays in multiple NSCLC cell lines. To identify possible targets of Raddeanin A in NSCLC, we employed a multifaceted approach incorporating network pharmacology, molecular docking, and molecular dynamics simulation, along with additional techniques such as SPR (Surface Plasmon Resonance), Co-IP (Co-Immunoprecipitation), and immunofluorescence. In vivo effects were investigated using a nude mouse xenograft tumor model.
Raddeanin A inhibits NSCLC cell survival, inhibits invasion and migration and causes cell cycle arrest in G1 phase. Raddeanin A impacts NSCLC cellular activity by inhibiting CDK6, leading to anti-tumor effects. Molecular analysis confirms that the tight binding between Raddeanin A and CDK6, facilitated by specific hydrogen bonds at binding sites including VAL-101, HIS-100, GLN-149, LYS-147, THR-182, VAL-180, and ALA-23, stabilizes within the 40-100 ns interval. In a nude mouse xenograft tumor model, Raddeanin A also demonstrated an inhibitory effect on NSCLC tumor growth.
Raddeanin A blocks the cell cycle in G1 phase by inhibiting CDK6. Raddeanin A is expected to be a novel antitumor agent against NSCLC.
本研究旨在探讨鸦胆子素A在体外和体内对非小细胞肺癌（NSCLC）的抗肿瘤作用及其机制。
通过流式细胞术和细胞生物学实验，评估鸦胆子素A对多种NSCLC细胞系的细胞周期进程、增殖、迁移和侵袭的影响。为了确定鸦胆子素A在NSCLC中的潜在靶点，我们采用了多方面的方法，包括网络药理学、分子对接和分子动力学模拟，以及表面等离子体共振（SPR）、免疫共沉淀（Co-IP）和免疫荧光等其他技术。使用裸鼠异种移植瘤模型研究其体内作用。
鸦胆子素A抑制NSCLC细胞存活，抑制侵袭和迁移，并使细胞周期停滞在G1期。鸦胆子素A通过抑制细胞周期蛋白依赖性激酶6（CDK6）影响NSCLC细胞活性，从而产生抗肿瘤作用。分子分析证实，鸦胆子素A与CDK6之间紧密结合，结合位点包括VAL-101、HIS-100、GLN-149、LYS-147、THR-182、VAL-180和ALA-23处的特定氢键促进了这种结合，在40-100纳秒的时间间隔内稳定存在。在裸鼠异种移植瘤模型中，鸦胆子素A对NSCLC肿瘤生长也表现出抑制作用。
鸦胆子素A通过抑制CDK6使细胞周期阻滞在G1期。鸦胆子素A有望成为一种新型的抗NSCLC抗肿瘤药物。
