1. Academic Validation
  2. Schisandrin B exerts anti-colorectal cancer effect through CXCL2/ERK/DUSP11 signaling pathway

Schisandrin B exerts anti-colorectal cancer effect through CXCL2/ERK/DUSP11 signaling pathway

  • Cancer Cell Int. 2025 Mar 15;25(1):97. doi: 10.1186/s12935-025-03727-9.
Jianguo Sun # 1 2 Zhipeng Wang # 1 Yunlei Yun # 1 Yingqi Feng 3 Zhijun Liu 1 Lili Cui 1 Mao Tang 1 Liya Ye 2 Zhengyan Liang 2 Wansheng Chen 4 Shouhong Gao 5 6
Affiliations

Affiliations

  • 1 Department of Pharmacy, Second Affiliated Hospital of Naval Medical University, No. 415, Fengyang Road, Shanghai, 200003, P. R. China.
  • 2 College of Traditional Chinese Medicine, Yunnan University of Traditional Chinese Medicine, Kunming, 650500, P. R. China.
  • 3 Guangzhou City Key Laboratory of Subtropical Fruit Tree Outbreak Control, Zhongkai University of Agriculture and Engineering, Guangzhou, 510225, P. R. China.
  • 4 Department of Pharmacy, Second Affiliated Hospital of Naval Medical University, No. 415, Fengyang Road, Shanghai, 200003, P. R. China. chenwansheng@smmu.edu.cn.
  • 5 Department of Pharmacy, Second Affiliated Hospital of Naval Medical University, No. 415, Fengyang Road, Shanghai, 200003, P. R. China. gaoshouhong@smmu.edu.cn.
  • 6 College of Traditional Chinese Medicine, Yunnan University of Traditional Chinese Medicine, Kunming, 650500, P. R. China. gaoshouhong@smmu.edu.cn.
  • # Contributed equally.
Abstract

Background: 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).

Method: 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.

Result: The Sch B showed obviously inhibitory effect to cell proliferation, invasion and migration of CRC cell lines with a IC50 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.

Conclusion: 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.

Keywords

CXCL2/ERK/DUSP11 axis; Colorectal cancer; Metabolomics; Schisandrin B; Transcriptomics.

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