2. Academic Validation
  3. Mechanism by which CAP regulates the "cold-heat" balance in osteosarcoma model mice: an integrative study of metabolomics, transcriptomics, and network pharmacology

Mechanism by which CAP regulates the "cold-heat" balance in osteosarcoma model mice: an integrative study of metabolomics, transcriptomics, and network pharmacology

  • J Transl Med. 2025 Oct 27;23(1):1177. doi: 10.1186/s12967-025-07238-z.
Ziming Wang 1,  Shun Zhang 2,  Shipeng Li 2,  Guosheng Zhao 3,  Yuan Zhang 4,  Xiaohong Zhang 2,  Mingwei Sun 2,  Yun Lu 1,  Enfeng Song 5,  Cantao Quan 6,  Chuanzhu Lv 7,  Yang Wang 8
Affiliations

Affiliations

  • 1 School of Clinical Medicine, Chengdu University of TCM, Emergency Department, Hospital of Chengdu University of TCM, Chengdu, 610036, China.
  • 2 Department of Emergency Medicine Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610064, China.
  • 3 Department of Orthopedic Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
  • 4 Department of Orthopedic Surgery, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, 400014, China.
  • 5 Department of TCM, Renmin Hospital of Wuhan University, Wuhan, China.
  • 6 The Sichuan Provincial Key Laboratory for Human Disease Gene Study, The Department of Medical Genetics, The Department of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
  • 7 Department of Emergency Medicine Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610064, China. lvchuanzhu677@126.com.
  • 8 Department of Emergency Medicine Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610064, China. young0416@163.com.
PMID: 41146125 DOI: 10.1186/s12967-025-07238-z
Abstract

Background: Osteosarcoma (OS) is a prevalent malignant bone Cancer in children and adolescents, yet the mechanisms driving its progression and therapeutic resistance remain inadequately understood. Current treatment modalities often overlook the significance of the “cold–heat” imbalance as conceptualized in traditional Chinese medicine (TCM), highlighting a critical gap in integrating TCM principles with modern Cancer therapies.

Objectives: We aimed to investigate the therapeutic effects of capsaicin (CAP) on the “cold–heat” imbalance in OS model mice and elucidate the mechanisms involved by utilizing a multiomics approach.

Methods: We employed metabolomics, transcriptomics, and network pharmacology to analyze the impact of CAP on OS progression. Tumor-bearing mice were treated with CAP, and metabolic profiles, tumor volumes, and key molecular targets were assessed.

Results: Our findings revealed that CAP significantly shifted the metabolic phenotype of OS model mice from a “cold” state to a “heat” state, resulting in a reduced tumor volume and increased metabolic activity. Notably, CAP was shown to target key pathways involving Akt1, STAT3, NF-κB, EGFR and Caspase 3.

Conclusion: CAP effectively modulated tumor growth and restored the “cold–heat” balance in OS model mice, providing valuable insights into the potential integration of TCM with conventional oncologic therapies. These findings underscore the importance of multifaceted strategies in developing innovative Cancer treatments and contribute to the advancement of translational medicine.

Graphical Abstract:

Supplementary Information: The online version contains supplementary material available at 10.1186/s12967-025-07238-z.

Keywords

CAP; Multiomics; OS; TCM; “cold-heat” balance.

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