PMID- 22808019
OWN - NLM
STAT- MEDLINE
DCOM- 20130326
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 7
DP  - 2012
TI  - Mirtazapine inhibits tumor growth via immune response and serotonergic system.
PG  - e38886
LID - 10.1371/journal.pone.0038886 [doi]
LID - e38886
AB  - 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-gamma 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-alpha 
      (TNF-alpha) 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.
FAU - Fang, Chun-Kai
AU  - Fang CK
AD  - Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming 
      University, Taipei, Taiwan.
FAU - Chen, Hong-Wen
AU  - Chen HW
FAU - Chiang, I-Tsang
AU  - Chiang IT
FAU - Chen, Chia-Chieh
AU  - Chen CC
FAU - Liao, Jyh-Fei
AU  - Liao JF
FAU - Su, Ton-Ping
AU  - Su TP
FAU - Tung, Chieh-Yin
AU  - Tung CY
FAU - Uchitomi, Yosuke
AU  - Uchitomi Y
FAU - Hwang, Jeng-Jong
AU  - Hwang JJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120713
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Adrenergic alpha-Antagonists)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 0 (Slc6a4 protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 187348-17-0 (Interleukin-12)
RN  - 250PJI13LM (Mianserin)
RN  - 82115-62-6 (Interferon-gamma)
RN  - A051Q2099Q (Mirtazapine)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Adrenergic alpha-Antagonists/pharmacology/*therapeutic use
MH  - Animals
MH  - Autoradiography
MH  - Colonic Neoplasms/*drug therapy/*immunology/pathology
MH  - Genes, Reporter
MH  - Immunity, Innate/*drug effects
MH  - *Immunocompromised Host
MH  - Injections, Subcutaneous
MH  - Interferon-gamma/biosynthesis/immunology
MH  - Interleukin-12/biosynthesis/immunology
MH  - Luciferases
MH  - Male
MH  - Mianserin/*analogs & derivatives/pharmacology/therapeutic use
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, SCID
MH  - Mirtazapine
MH  - Neoplasm Transplantation
MH  - Serotonin Plasma Membrane Transport Proteins/*agonists/metabolism
MH  - Survival Rate
MH  - T-Lymphocytes/drug effects/immunology
MH  - Tumor Microenvironment/drug effects
MH  - Tumor Necrosis Factor-alpha/biosynthesis/immunology
PMC - PMC3396612
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/07/19 06:00
MHDA- 2013/03/27 06:00
PMCR- 2012/07/13
CRDT- 2012/07/19 06:00
PHST- 2011/12/16 00:00 [received]
PHST- 2012/05/14 00:00 [accepted]
PHST- 2012/07/19 06:00 [entrez]
PHST- 2012/07/19 06:00 [pubmed]
PHST- 2013/03/27 06:00 [medline]
PHST- 2012/07/13 00:00 [pmc-release]
AID - PONE-D-11-25280 [pii]
AID - 10.1371/journal.pone.0038886 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(7):e38886. doi: 10.1371/journal.pone.0038886. Epub 2012 Jul 13.