Identification for antitumor effects of tramadol in a xenograft mouse model using orthotopic breast cancer cells

• Published in: Scientific reports Vol. 11; no. 1; p. 22113
• Main Authors: Kim, Myoung Hwa, Lee, Jeong-Rim, Kim, Ki-Joon, Jun, Ji Hae, Hwang, Hye Jeong, Lee, Wootaek, Nam, Seung Hyun, Oh, Ju Eun, Yoo, Young Chul
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.11.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/67; 692/4028; Animals; Antineoplastic Agents - pharmacology; Antitumor activity; Bioluminescence; Breast - drug effects; Breast - metabolism; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Capsaicin receptors; Cell Line, Tumor; Cytokines; Disease Models, Animal; Estrogen receptors; Estrogens; Female; Heterografts - drug effects; Humanities and Social Sciences; Humans; Interferon; Interleukin 6; Killer Cells, Natural - drug effects; Killer Cells, Natural - metabolism; Luciferin; MCF-7 Cells; Mice; Mice, Inbred BALB C; Mice, Nude; Morphine; Morphine - pharmacology; multidisciplinary; Natural killer cells; Progesterone; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; Science; Science (multidisciplinary); Serum levels; Tramadol; Tramadol - pharmacology; Transient receptor potential proteins; Transplantation, Heterologous - methods; TRPV Cation Channels - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Tumors; Xenografts
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-01701-9

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 .