Sun Jianguo, Wang Zhipeng, Yun Yunlei, Feng Yingqi, Liu Zhijun, Cui Lili, Tang Mao, Ye Liya, Liang Zhengyan, Chen Wansheng, Gao Shouhong
Department of Pharmacy, Second Affiliated Hospital of Naval Medical University, No. 415, Fengyang Road, Shanghai, 200003, P. R. China.
College of Traditional Chinese Medicine, Yunnan University of Traditional Chinese Medicine, Kunming, 650500, P. R. China.
Cancer Cell Int. 2025 Mar 15;25(1):97. doi: 10.1186/s12935-025-03727-9.
Schisandrin B (Sch B) is an active component in Schisandra chinensis exerting anti-cancer effect, but the mechanism is obscure. This study was designed to explore the mechanism of Sch B against colorectal cancer (CRC).
Apparent experiments including cell proliferation, transwell, colony formation, etc. were carried out to assess the anti-cancer effect of Sch B to CRC cell lines, and the RNA-seq was performed prior to bioinformatics analysis to explore the key transcriptome alterations, furthermore, an untargeted metabolomics was carried out to profile the metabolic alterations after the treatment with Sch B and an integrated analysis and experiment validation were completed based on RNA-seq and metabolomics to find the critical mechanism.
The Sch B showed obviously inhibitory effect to cell proliferation, invasion and migration of CRC cell lines with a IC value at 75 µM. The RNA-seq and bioinformatics analysis found the ERK/MAPK pathway has been significantly suppressed by the Sch B treatment, while the chemokine, CXCL2, could activate the ERK pathway when binding to its receptor CXCR2. The metabolomics revealed the metabolic profile of CRC cell was remarkably influenced by the Sch B, focusing on the arginine and proline metabolism, ubiquinone, etc. Importantly, the integrated analysis found the DUSP11 connected the ERK pathway and the metabolisms, may mediate the anti-cancer effect of Sch B.
Sch B showed obviously anti-cancer effect to the CRC through inhibiting CXCL2/ERK/DUSP11 axis, but more experiments are needed to figure out the target of Sch B and validate this mechanism in vivo.
五味子乙素（Sch B）是五味子中的一种活性成分，具有抗癌作用，但其机制尚不清楚。本研究旨在探讨Sch B抗结直肠癌（CRC）的机制。
进行细胞增殖、Transwell、集落形成等表观实验，以评估Sch B对CRC细胞系的抗癌作用，并在进行生物信息学分析之前进行RNA测序，以探索关键的转录组改变。此外，进行非靶向代谢组学分析，以描绘Sch B处理后的代谢变化，并基于RNA测序和代谢组学完成综合分析和实验验证，以找到关键机制。
Sch B对CRC细胞系的细胞增殖、侵袭和迁移具有明显的抑制作用，IC值为75 μM。RNA测序和生物信息学分析发现，Sch B处理显著抑制了ERK/MAPK通路，而趋化因子CXCL2与其受体CXCR2结合时可激活ERK通路。代谢组学显示，Sch B显著影响了CRC细胞的代谢谱，主要集中在精氨酸和脯氨酸代谢、泛醌等方面。重要的是，综合分析发现DUSP11连接了ERK通路和代谢过程，可能介导了Sch B的抗癌作用。
Sch B通过抑制CXCL2/ERK/DUSP11轴对CRC显示出明显的抗癌作用，但需要更多实验来明确Sch B的靶点并在体内验证该机制。
