Effect of antidepressants on body weight, ethology and tumor growth of human pancreatic carcinoma xenografts in nude mice

AIM： To investigate the effects of mirtazapine and fluoxetine, representatives of the noradrenergic and specific serotonergic antidepressant （NaSSA） and se- lective serotonin reuptake inhibitor （SSRI） antidepres- sant respectively, on body weight, ingestive behavior, locomotor activity and tumor growth of human pancre- atic carcinoma xenografts in nude mice. METHODS： A subcutaneous xenograft model of hu- man pancreatic cancer cell line SW1990 was estab- lished in nude mice. The tumor-bearing mice were ran- domly divided into mirtazapine group [10 mg/（kg·d）], fluoxetine group [10 mg/（kg·d）] and control group （an equivalent normal saline solution） （7 mice in each group）. Doses of all drugs were administered orally, once a day for 42 d. Tumor volume and body weight were measured biweekly. Food intake was recorded once a week. Locomotor activity was detected weekly using an open field test （OFT）. RESULTS： Compared to the fluoxetine, mirtazapine significantly increased food intake from d 14 to 42 and attenuated the rate of weight loss from d 28 to 42 （t = 4.38, P 〈 0.05）. Compared to the control group, food intake was significantly suppressed from d 21 to 42 and weight loss was promoted from d 35 to 42 in the fluoxetine group （t = 2.52, P 〈 0.05）. There was a significant difference in body weight of the mice after removal of tumors among the three groups. The body weight of mice was the heaviest （13.66 ± 1.55 g） in the mirtazapine group and the lightest （11.39 ± 1.45 g） in the fluoxetine group （F（2,12） = 11.43, P 〈 0.01）. The behavioral test on d 7 showed that the horizontal and vertical activities were significantly increased in the mirtazapine group compared with the fluoxetine and control groups （F（2,18） = 10.89, P 〈 0.01）. These effects disappeared in the mirtazapine and fluoxetine groups during 2-6 wk. The grooming activity was higher in the mirtazapine group than in the fluoxetine group （10.1 ± 2.1 vs 7.1 ± 1.9 ） （t = 2.40, P 〈 0.05） in the second week. There was no significant difference in tumor vol- ume and tumor weight of the three groups. CONCLUSION： Mirtazapine and fluoxetine have no effect on the growth of pancreatic tumor. However, mirtazapine can significantly increase food intake and improve nutrition compared with fluoxetine in a pan- creatic cancer mouse model.