Mirtazapine inhibits tumor growth via immune response and serotonergic system.
To study the tumor inhibition effect of mirtazapine, a drug for patients with depression, CT26/luc colon carcinoma-bearing animal model was used. BALB/c mice were randomly divided into six groups: two groups without tumors, i.e. wild-type (no drug) and drug (mirtazapine), and four groups with tumors, i.e. never (no drug), always (pre-drug, i.e. drug treatment before tumor inoculation and throughout the experiment), concurrent (simultaneously tumor inoculation and drug treatment throughout the experiment), and after (post-drug, i.e. drug treatment after tumor inoculation and throughout the experiment). The "psychiatric" conditions of mice were observed from the immobility time with tail suspension and spontaneous motor activity post tumor inoculation. Significant increase of serum interleukin-12 (sIL-12) and the inhibition of tumor growth were found in mirtazapine-treated mice (always, concurrent, and after) as compared with that of never. In addition, interferon-γ level and immunocompetent infiltrating CD4+/CD8+ T cells in the tumors of mirtazapine-treated, tumor-bearing mice were significantly higher as compared with that of never. Tumor necrosis factor-α (TNF-α) expressions, on the contrary, are decreased in the mirtazapine-treated, tumor-bearing mice as compared with that of never. Ex vivo autoradiography with [(123)I]ADAM, a radiopharmaceutical for serotonin transporter, also confirms the similar results. Notably, better survival rates and intervals were also found in mirtazapine-treated mice. These findings, however, were not observed in the immunodeficient mice. Our results suggest that tumor growth inhibition by mirtazapine in CT26/luc colon carcinoma-bearing mice may be due to the alteration of the tumor microenvironment, which involves the activation of the immune response and the recovery of serotonin level.
Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
Chun-Kai
CK
Fang
Hong-Wen
HW
Chen
I-Tsang
IT
Chiang
Chia-Chieh
CC
Chen
Jyh-Fei
JF
Liao
Ton-Ping
TP
Su
Chieh-Yin
CY
Tung
Yosuke
Y
Uchitomi
Jeng-Jong
JJ
Hwang
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001345:Autoradiography; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D017930:Genes, Reporter; D007113:Immunity, Innate / Q000187:drug effects*; D016867:Immunocompromised Host; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D008156:Luciferases; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D000078785:Mirtazapine; D009368:Neoplasm Transplantation; D050486:Serotonin Plasma Membrane Transport Proteins / Q000819:agonists* / Q000378:metabolism; D015996:Survival Rate; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D059016:Tumor Microenvironment / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
D000317:Adrenergic alpha-Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D008803:Mianserin; D007371:Interferon-gamma; D000078785:Mirtazapine; D008156:Luciferases