ArticleNaunyn-Schmiedeberg's archives of pharmacology2024
Tramadol suppresses growth of orthotopic liver tumors via promoting M1 macrophage polarization in the tumor microenvironment.
Article in Naunyn-Schmiedeberg's archives of pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 6 citations in OpenAlex.
- Traditional Chinese medicine formula Xiang Bei San suppresses the growth and metastasis of breast cancer by regulating macrophage polarization and tumor vascularization.Journal of natural medicines · 2026Article
- Improving pain management for murine orthotopic xenograft models of acute lymphoblastic leukemia.Lab animal · 2025Article
- Research progress on the impact of opioids on the tumor immune microenvironment (Review).Molecular and clinical oncology · 2025Review
- Regulation and Crosstalk of Cells and Factors in the Pancreatic Cancer Microenvironment.Current cancer drug targets · 2025Review
- Hydrogel systems for spatiotemporal controlled delivery of immunomodulators: engineering the tumor immune microenvironment for enhanced cancer immunotherapy.Frontiers in cell and developmental biology · 2024Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor-associated macrophages (TAMs) are major infiltrating immune cells in liver cancer. They are polarized to anti-tumor M1 type or tumor-supporting M2 type in a dynamic changing state. Tramadol, a synthetic opioid, exhibits tumor-suppressing effect in several cancers, but whether it plays a role in TAMs polarization is uncertain. In the present study, the potential influence of tramadol on TAMs polarization was explored in liver cancer. An orthotopic murine Hepa 1-6 liver cancer model was constructed. The potential function of tramadol was evaluated by cell viability assay, EdU incorporation assay, flow cytometry, immunofluorescence, quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA) assay, T cell proliferation and suppression assays and western blot. We found that tramadol suppressed proliferation and tumor formation of murine Hepa 1-6 cells in vitro and in vivo. Tramadol reprogramed the immune microenvironment to favor M1 macrophage polarization in orthotopic Hepa 1-6 tumors. Moreover, tramadol facilitated M1 macrophage polarization and inhibited M2 macrophage polarization of bone marrow-derived macrophages (BMDMs) and human THP-1 macrophages in vitro. Furthermore, tramadol-treated BMDMs promoted proliferation and activation of splenic CD4
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