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Updated: Oct 13, 2025
Orthotopic Injection of Breast Cancer Cells into the Mice Mammary Fat Pad
Published on: January 20, 2019
Identification for antitumor effects of tramadol in a xenograft mouse model using orthotopic breast cancer cells
Myoung Hwa Kim1, Jeong-Rim Lee2, Ki-Joon Kim2
1Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Gangnam Severance Hospital, Gangnam-gu, Seoul, 06273, Republic of Korea.
Abstract:
In our previous research showed that tramadol having potential anti-tumor effect was associated with enhancement of oncological prognosis in patients with breast cancer surgery. As these effects have not been confirmed by clinical dose-regulated animal or prospective human studies, we investigated the anti-tumor effect of tramadol in vivo. Female nude mice orthotopically inoculated with luciferase-expressing MCF-7 cells, were randomly divided into the control (saline), tramadol group 1 (1.5 mg kg-1 day-1), tramadol group 2 (3 mg kg-1 day-1), and morphine (0.5 mg kg-1 day-1) (n = 5/group). Bioluminescence signals after D-luciferin injection, tumor size, and tumor weight were compared among groups after 4 weeks. Estrogen receptor (ER), progesterone receptor (PR), and transient receptor potential vanilloid (TRPV)-1 expression, natural killer (NK) cell activity, and serum interleukin (IL)-1β, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-6 were then examined. Tumour growth was attenuated in tramadol-treated groups (P < 0.05). NK cell activity was significantly decreased only in the morphine treated group not in sham, control, and tramadol groups. The expression levels of ERα, PRα and β, and TRPV1 were decreased in tramadol group 2 compared with those in the morphine group, but not compared to the control group. Serum levels of IL-6 and TNFα were reduced in both tramadol-treated group 1 and 2 compared to the control group. Overall, clinical dose of tramadol has anti-tumour effects on MCF-7 cell-derived breast cancer in a xenograft mouse model.
Insights
Tramadol demonstrated anti-tumor effects in a mouse model of breast cancer, reducing tumor growth and inflammation. Unlike morphine, tramadol did not impair natural killer cell activity, suggesting a safer therapeutic profile.
Area of Science:
- Oncology
- Pharmacology
- Immunology
Background:
- Previous research suggested tramadol may enhance oncological prognosis in breast cancer patients.
- Clinical validation through dose-regulated animal or prospective human studies was lacking.
Purpose of the Study:
- To investigate the in vivo anti-tumor effect of tramadol in a breast cancer xenograft mouse model.
- To compare tramadol's effects with morphine and assess its impact on tumor growth, immune markers, and receptor expression.
Main Methods:
- Female nude mice bearing MCF-7 breast cancer xenografts were treated with tramadol (1.5 or 3 mg/kg/day), morphine (0.5 mg/kg/day), or saline.
- Tumor growth, bioluminescence, immune cell activity (NK cells), and serum cytokine levels (IL-1β, TNF-α, IFN-γ, IL-6) were analyzed.
- Expression of estrogen receptor (ER), progesterone receptor (PR), and TRPV1 was examined.
Main Results:
- Tramadol treatment significantly attenuated tumor growth in both dose groups (P < 0.05).
- Natural killer (NK) cell activity decreased with morphine but not tramadol.
- Tramadol reduced serum IL-6 and TNF-α levels and decreased ER, PR, and TRPV1 expression compared to morphine.
Conclusions:
- Clinical doses of tramadol exhibit anti-tumor effects in a mouse model of MCF-7 breast cancer.
- Tramadol appears to have a more favorable immunomodulatory profile than morphine in this model.
- These findings support further investigation into tramadol's therapeutic potential in breast cancer treatment.
