Intervention of mirtazapine on gemcitabine-induced mild cachexia in nude mice with pancreatic carcinoma xenografts

World J Gastroenterol. 2012 Jun 14;18(22):2867-71. doi: 10.3748/wjg.v18.i22.2867.


Aim: To investigate the effect of mirtazapine on tumor growth, food intake, body weight, and nutritional status in gemcitabine-induced mild cachexia.

Methods: Fourteen mice with subcutaneous xenografts of a pancreatic cancer cell line (SW1990) were randomly divided into mirtazapine and control groups. Either mirtazapine (10 mg/kg) or saline solution was orally fed to the mice every day after tumor implantation. A model of mild cachexia was then established in both groups by intraperitoneal injection of gemcitabine (50 mg/kg) 10 d, 13 d, and 16 d after tumor implantation. Tumor size, food intake, body weight, and nutritional status were measured during the experiment. All mice were sacrificed at day 28.

Results: (1) After 7 d of gemcitabine administration, body-weight losses of 5%-7% which suggested mild cachexia were measured; (2) No significant difference in tumor size was detected between the mirtazapine and control groups (P > 0.05); and (3) During the entire experimental period, food intake and body weight were slightly greater for the mirtazapine group compared with controls (although these differences were not statistically significant). After 21 d, mice in the mirtazapine group consumed significantly more food than control mice (3.95 ± 0.14 g vs 3.54 ± 0.10 g, P = 0.004). After 25 d, mice in the mirtazapine group were also significantly heavier than control mice (17.24 ± 0.53 g vs 18.05 ± 0.68 g, P = 0.014).

Conclusion: Mild cachexia model was successfully established by gemcitabine in pancreatic tumor-bearing mice. Mirtazapine can improve gemcitabine-induced mild cachexia in pancreatic tumor-bearing mice. It was believed to provide a potential therapeutic perspective for further studies on cachexia.

Keywords: Antidepressant; Cachexia; Gemcitabine; Mirtazapine; Pancreatic carcinoma.

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / toxicity*
  • Body Weight / drug effects
  • Cachexia / chemically induced
  • Cachexia / physiopathology
  • Cachexia / prevention & control*
  • Carcinoma / drug therapy*
  • Carcinoma / pathology
  • Cell Line, Tumor
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / toxicity
  • Eating / drug effects
  • Humans
  • Mianserin / analogs & derivatives*
  • Mianserin / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mirtazapine
  • Nutritional Status / drug effects
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology
  • Time Factors
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays


  • Antimetabolites, Antineoplastic
  • Deoxycytidine
  • Mianserin
  • Mirtazapine
  • gemcitabine